physiologic basis of potentials recorded in electromyography

SCIENCE SEMINARFOR CLINICIANS

ABSTRACT: The extracellularly recorded configuration of a single musclefiber discharge is generally appreciated to be triphasic with an initially posi-tive deflection. However, careful attention to waveform appearance duringthe electrodiagnostic medicine examination reveals that both innervated anddenervated muscle waveforms may display a pantheon of configurations.Further, despite the fact that innervated and denervated single muscle fiberdischarges arise from distinctly different intracellular action potential (IAP)configurations, their extracellularly recorded waveforms can appear quitesimilar, leading to potential misidentification and, hence, the possibility of anerroneous diagnostic conclusion. The least appreciated, but neverthelesscritical, aspect of explanations for muscle waveform configurations is therelationship between the muscle fiber and recording electrode. Additionally,it is important to appreciate both the near-field and far-field aspects of singlefiber and compound muscle action potentials. In this review, the leading/trailing dipole model is used to explain muscle waveform configurations inboth innervated and denervated tissues.

© 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 1667–1685, 2000

PHYSIOLOGIC BASIS OF POTENTIALSRECORDED IN ELECTROMYOGRAPHY

DANIEL DUMITRU, MD, PhD

Department of Rehabilitation Medicine, University of Texas Health Science Centerat San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA

Accepted 24 May 2000

An explanation for the configuration of extracellu-larly recorded single muscle fiber discharges is not atrivial matter. A true understanding of this topic re-quires an in-depth knowledge of a branch of physicsknown as electrodynamics which is commonly re-ferred to in electrodiagnostic medicine as “volumeconductor theory.” It is certainly possible, however,to gain a good qualitative clinical appreciation ofextracellular waveform configuration by using de-ceptively simple models. It may appear as thoughattempting to understand why an endplate spike ap-pears as it does compared to a positive sharp wave,for example, is primarily of academic interest only.However, basic knowledge of “volume conductortheory” can explain a number of clinical situations

that may appear confusing. An overview of sponta-neous single muscle fiber discharges for both inner-vated and denervated muscle tissue will be addressedin an attempt to convey a fuller appreciation of thesewaveforms.

NORMAL MUSCLE

Intracellular Potentials. Resting Membrane Poten-tial. It is generally appreciated that all cells in thebody establish and maintain a transmembrane po-tential which is stable over time, i.e., a resting mem-brane potential (RMP). The distinguishing charac-teristic of an excitable cell, however, is that it has theability to generate a propagating wave of depolariza-tion, i.e., an action potential.

There are three primary ionic species in the ex-tracellular medium: sodium (Na+) and potassiumions (K+) which are positively charged (cations) andchloride (Cl−) ions which are negatively charged(anions).9,16,46 Intracellularly, negatively chargednon-diffusable compounds attract both the sodiumand potassium ions. However, at the RMP, only thepotassium and chloride ions are capable of travers-ing the cell membrane to any extent with a smalldegree of sodium permeability present.3 If an elec-trode is located intracellularly while another elec-trode is positioned extracellularly, and both are con-

Abbreviations: ACh, acetylcholine; ADM, abductor digiti minimi; APB,abductor pollicis brevis; ATP, adenosine triphosphate; CMAP, compoundmuscle action potential; EMG, electromyography; EPS, endplate spike;Fibs, fibrillation potentials; HPP, hyperkalemic periodic paralysis; IAP, in-tracellular action potential; LD, leading dipole; L/TD, leading training di-pole; MEPP, miniature endplate potential; MUAP, motor unit action poten-tial; PAM, potassium aggravated myotonia; PMC, paramyotoniacongenita; PROMM, proximal myotonic myopathy; PSW, positive sharpwave; RMP, resting membrane potential; T-system, transverse tubule sys-tem; TD, trailing dipole; TTX, tetrodotoxinKey words: endplate spikes; fibrillation potentials; myotonic discharge;positive sharp waves; single muscle fiber dischargeCorrespondence to: D. Dumitru. e-mail: [email protected]

© 2000 John Wiley & Sons, Inc.

Muscular Waveform Configuration MUSCLE & NERVE November 2000 1667

nected to a voltmeter, a potential difference of about80 mV may be measured, with the inside of the cellrelatively negative compared to the extracellularspace.38 This balance of equilibrium (equilibriumpotential of about −80 mV) between electrical andconcentration forces for the potassium ion, particu-larly for excitable cells, occurs with the cell in its“resting” state. Therefore, the cell’s RMP is said toapproximate the resting or equilibrium electrical po-tential for the potassium ion, i.e., about −80mV.35,38,46

The chloride ion (Cl−) is also in abundance witha high extracellular and low intracellular concentra-tion.57 This ion carries a net negative charge. Be-cause the intracellular environment is also negative,a significant repulsive force attempts to preclude anynegative ions from entering the cell. Nevertheless,with the high extracellular concentration of chlorideion present, a small amount does enter the cell.There are voltage-gated chloride ion channels in thecell’s membrane that permit this ionic species to dis-tribute or alter its intracellular concentration de-pending upon shifts of potassium and sodium and,hence, the transmembrane potential.44 These chlo-ride channels are open at the RMP. In this sense, thechloride ion is often said to be “passively” distrib-uted. This does not mean, however, that it is notimportant or has little impact on the cell’s electricalfunctioning. The chloride ion has a clinical impactin some of the disorders producing myotonic dis-charges (see below).

Although all of the above information was ini-tially described for neural tissue, it applies equallywell for muscle tissue.38,57 Nevertheless, slight ionicdifferences exist between the exact concentrationsof different ions between cell types, within a singlespecies, and between the similar cell types in differ-ent species.

Action Potential. Excitable tissues (nerve andmuscle) have the ability to generate a traveling re-versal in the transmembrane voltage along theirlength. It is this propagating transmembrane rever-sal of voltage that is referred to as an action poten-tial. The generation of this action potential and itsaccompanying configuration are important to un-derstand because it is the extracellular waveformmanifestation of the transmembrane voltage reversalprocess that is detected during the electrodiagnosticmedicine examination for both nerve and muscletissue.

If a small amount of positive ions such as sodium,in excess of that capable of being removed quickly bythe sodium-potassium adenosine triphosphate(ATP)-dependent pump are injected intracellularly,

the RMP becomes less negative, e.g., it depolarizes to−70 mV. Adding slightly more positive ions results ina further membrane depolarization. Injectingenough sodium ions so as to reduce the RMP toabout −50 to −65 mV results in a rapid alteration inthe transmembrane voltage to approximately +40mV (Fig. 1).19,39,40,41 Shortly thereafter, the trans-membrane potential begins to repolarize, but at amuch slower rate than that of depolarization. Even-tually, the RMP is again established.

At approximately −50 to −65 mV, there is a pre-cipitous increase in the membrane’s permeability(conductance) to the sodium ion, referred to as so-dium activation (Fig. 1A,B). This permeability isshort-lived (<1 ms in muscle) and rapidly declinessecondary to sodium inactivation. Shortly after theincrease in sodium conductance, potassium activa-tion also occurs (Fig. 1A,B). Peak potassium perme-ability occurs somewhat later than sodium perme-

FIGURE 1. (A) Alterations in Na+ conductance (gNa) abovethreshold results in depolarization, whereas increased K+ con-ductance (gK) helps reestablish the RMP. The net result of thesetwo processes is a monophasic positive intracellular action po-tential. (B) Transmembrane dipolar arrangement of intracellularand extracellular ions is depicted. (C) Directional arrows indicatethe flow of sodium ion comprising the local circuit currents. Flowof sodium ions is from those regions surrounding the open so-dium channels into the cell’s interior, and then proceeds bidirec-tionally to complete the current flow. (D) A triphasic extracellularwaveform results from the above local circuit currents in a goodvolume conductor such as the body. (From Dumitru19 with per-mission.)

1668 Muscular Waveform Configuration MUSCLE & NERVE November 2000

ability.49 It is the combination of a rapid decline insodium permeability and an increase in potassiumpermeability that precludes the transmembrane volt-age from reaching the equilibrium potential of thesodium ion (+67 mV) as would be predicted by theNernst equation. The increase in both sodium andpotassium permeability is mediated by voltage-gatedsodium and potassium channels, respectively. Thesechannels are different than the ion channels whichare open at the resting level of −80 mV, i.e., nonvolt-age-gated ion channels. During this process, thechloride ion through its own transmembrane volt-age-gated channel is distributed accordingly with re-spect to the intracellular potential. The action po-tential’s intracellular voltage profile is monophasic(−80 mV → +44 mV → −80 mV) and referred to as“positive” because it changes from a negative to a posi-tive, and back to a negative voltage level (Fig. 1A).

Local Circuit Currents. Following any mechani-cal, electrical, or chemical stimuli that results in atransmembrane shift to the threshold value, theabove-noted sequence of activating and inactivatingsodium and potassium voltage-gated channels oc-curs. Any shift in transmembrane voltage is directlydependent upon the actual flow of sodium ions intothe cell (Fig. 1C). The sodium ion is positivelycharged and enters the cell because of both the elec-trical (intracellularly negative) and concentration(greater extracellularly) gradients favor this direc-tional flow. Since a positive ion is moving, it consti-tutes charge movement and is equivalent to a cur-rent flow.38 That region of membrane where inwardpositive current flow occurs is referred to as a “cur-rent sink.” The current sink is designated with a rela-tive negative voltage because the positive sodiumions are attracted to a region of relatively less posi-tivity, i.e., a more negative region. That region of theextracellular space from which positive sodium ionsare being drawn is referred to as a current sourceand designated with a relative positive voltage (withrespect to the negative sink).

As viewed from the cell’s exterior, the intracellu-lar action potential is comprised of a “negative” cen-tral current sink surrounded by “positive” currentsources. The extracellular current flows and theirassociated intracellular counterpart current flowsare referred to as local circuit currents and form thebasis for the action potential’s extracellular configu-ration (Fig. 1D).38 Because nerve and muscle tissueare essentially extended cylinders, in a two-dimensional view of an action potential extendingalong the tissue, the central negative current sinkappears flanked by two positive current sources. Anaction potential is often therefore described as a

“source-sink-source.” This designation is often re-written in a form of shorthand designating theequivalent voltages (+ − +) or called a “tripole.”65,66

Action potentials propagate secondary to the re-petitive process of one region of membrane depo-larizing the next membrane region. Implicit in ac-tion potential propagation is the concept ofdirection. That is, an action potential originates atone point and propagates to another. Therefore, theaction potential can be considered to have a leadingportion and a trailing portion. For convenience, theabove-noted tripole is commonly rewritten by con-sidering direction and splitting the central negativesink into two negative regions, each of which is as-sociated with a leading or a trailing current source,referred to as quadrupole: (+ − − +).65 One of thepositive current sources and its associated negativecurrent sink is designated the leading dipole (LD; +−), and the other positive source and its associatednegative current sink is designated the trailing di-pole (TD; − +). The designations “leading” and“trailing” are obviously dependent upon which di-rection the action potential’s subcomponent dipolesare traveling. When an action potential is describedas being comprised of a leading and trailing dipole,it is referred to not as a tripole but a quadrupole.The dipole model using leading and trailing dipolesis known as the leading/trailing dipole model (L/TD model).20

L/TD Model. The L/TD model is a relativelyeasy way to think about action potentials, yet pro-vides a powerful tool for the practitioner to gainsignificant insight into why potentials appear as theydo. Simply, an electrode located in the vicinity ofeither the LD or TD positive pole will record a posi-tive deflection on the electrodiagnostic instrument.Similarly, when the recording electrode is in the vi-cinity of the quadrupole’s negative poles, a negativeoscilloscope deflection will be documented. This isthe essence of the L/TD model. The nuances of thismodel will be explored in more detail with respect toeach specific waveform considered.

Recording Electrode and Tissue Effects. Inserting amonopolar or concentric needle electrode intomuscle tissue results in adverse anatomic31 as well aselectrical effects.51 Histologic assessment of muscletissue following needle insertion reveals muscle fiberdisruption as well a reactive inflammatory response.A portion of the needle electromyographic exami-nation actually takes advantage of the fact that theneedle electrode mechanically depolarizes the tis-sue. Needle “insertional activity” is routinely assessedto determine whether the muscle membrane dem-onstrates any degree of instability with respect to


provoking positive sharp waves and fibrillation po-tentials.51,79–81 Attempts have been made to describeinsertional activity as normal, increased, or de-creased.

Recording Electrode and Waveform Morphology.Perhaps the most poorly appreciated interaction be-tween the needle recording electrode and themuscle fiber is the direct influence the electrode hason waveform configuration. It is generally assumedthat the monopolar or concentric needle electrodeis simply a passive bystander merely recording whatever electrical activity is within its pickup area. A num-ber of investigations have suggested that, to the con-trary, a dynamic interplay exists between the needleelectrode and the muscle fiber, directly influencingthe recorded waveform’s configuration.21,22,25,26,28

SINGLE MUSCLE FIBER DISCHARGES

Miniature Endplate Potentials. The endplate orneuromuscular junction region is that specializedportion of the muscle fiber where a terminal nervefiber interfaces with the muscle fiber. At rest, theneurotransmitter acetylcholine (ACh) is spontane-ously released a few quanta at a time.29,30 Thisamount of ACh is insufficient to open enough ACh-gated receptor channels to reach the adjacent mem-brane’s threshold level for voltage-gated sodiumchannel activation. That is, the small amount oftransmitter released only produces a small or so-called miniature endplate potential (MEPP), as op-posed to an endplate potential which is the summa-tion of multiple MEPPs. However, the amount ofsodium ions that do enter the postsynaptic portionof the muscle fiber results in a small depolarizingcurrent which can be detected with an extracellu-larly located electrode.74

When the subthreshold amount of ACh is re-leased and the ACh receptor channels permit so-dium ions to flow into the muscle fiber, a negativecurrent sink is formed surrounded by currentsources. However, the amount of sodium is insuffi-cient to reach the muscle membrane’s thresholdlevel and open voltage-gated sodium channels, sothe quadrupole dissipates instead of propagating. Ifan electrode is positioned directly over the endplateregion and hence over the negative current sink, asmall (∼50 µV or less) negative spike is detected.However, failure of action potential initiation im-plies that as the quadrupole dissipates, so does thenegative spike. In this case, there really is no leadingor trailing dipole because the induced action poten-tial does not propagate. The end result is a mono-phasic negative spike typically causing a small rip-pling of the electrodiagnostic instrument’s baseline.

It is these subthreshold monophasic negative poten-tials that are commonly referred to as endplate noiseor the so-called sea shell murmur.11

Endplate Spike. An endplate spike is the extracel-lularly recorded single muscle fiber discharge initi-ated when a sufficient number of MEPPs summate togenerate a suprathreshold endplate potential.82 Theinitiating factor in endplate spike generation is be-lieved to be the needle electrode “irritating” amuscle fiber’s terminal nerve or endplate region,most likely through physical contact. The dischargefrequency of endplate spikes approximates 19 HZ

and is highly irregular.74 Endplate spike frequenciescan reach 50–60 HZ (personal observation), in whichcase they may seem regular.

Prototypical Endplate Spike Configuration. It isgenerally accepted that the prototypical endplatespike is a biphasic, initially negative waveform, i.e., acomparatively large initial negative deflection fol-lowed by a relatively small terminal positive phase.11

The L/TD model can be utilized to understand thisconfiguration.

Let us assume the needle electrode (designatedE-1 for the active recording electrode) is purpose-fully positioned directly over a single muscle fiber’sendplate region and physically irritates the terminalnerve fiber or endplate for this fiber. The ensuingrelease of ACh results in an increased membranepermeability to sodium, creating a developing actionpotential’s current sink and surrounding currentsources, i.e., a developing quadrupole (Fig. 2A;E-1A). The extracellularly located needle electrodedetects a growing negative voltage associated withthe action potential’s developing negative currentsink and displays a negative waveform deflection ofincreasing magnitude. The quadrupole increases inmagnitude and begins to propagate along the fiberin both directions away from the endplate region(Fig. 2B–C; E-1A); its negative sink region movesaway from the electrode and onto the muscle fiber.This permits the electrode to detect the quadru-pole’s terminal dipole, in particular its positive pole(Fig. 2C; E-1A) and subsequently displays a terminalpositive phase. Continued action potential propaga-tion along the muscle fiber implies the terminal di-pole is moving further from the electrode and,hence, its associated terminal positive phase declinesin magnitude (Fig. 2E; E-1A). The end result of thisprocess is a biphasic, initially negative waveform, as isobserved clinically (Fig. 3A).

“Atypical” Triphasic Endplate Spike Configuration.The needle electrode will not always take a route inwhich it is perpendicular to the endplate region.


Therefore, the needle electrode may sometimes ap-proach a single muscle fiber’s endplate region some-what tangentially; its shaft still irritates the terminalnerve, but its active recording surface contacts themuscle fiber at some distance from the endplate re-

gion. This type of recording situation places the nee-dle’s recording surface at a distance from the form-ing quadrupole at the endplate region (Fig. 2A–H;E-1B). Hence, the needle electrode does not detectthe quadrupole’s negative current sink, but insteadfirst records the leading dipole of the quadrupole,resulting in a positive voltage. As the quadrupolepropagates toward the electrode, a waveform with aninitial positive deflection is documented. Arrival ofthe negative sink at the electrode generates the ex-pected negative deflection. Finally, departure of thequadrupole from the electrode’s location results inthe electrode detecting the trailing dipole’s terminalpositive pole, creating a positive waveform deflec-tion. The final waveform is triphasic with an initialpositive deflection.

The magnitude and temporal duration of the ini-tial positive deflection depends upon the distancefrom the endplate zone. Simulation studies suggestthat when an electrode situated directly over, orwithin about 200 µm from the endplate zone, aninitial negative deflection is detected.27 Beyond thisdistance, the endplate spike manifests with an initialpositive deflection. It is the author’s experience thattriphasic endplate spikes are rather common, butthey have received little attention (Fig. 3B). In real-ity, the configuration of triphasic endplate spikesand fibrillation potentials are identical since they areboth single muscle fiber discharges recorded outsideof the endplate zone. The distinction of endplatespikes from fibrillation potentials is based on respec-tive firing rates. Fibrillation potentials usually dem-onstrate a discharge frequency of about 6–10 HZ andfire very regularly, whereas endplate spikes usuallyfire at higher frequencies (19 HZ) and quite irregu-larly (Table 1).74 Nevertheless, it is not always easy totell the difference between endplate spikes and fi-

FIGURE 3. (A) Prototypical biphasic initially negative endplatespikes recorded with a monopolar electrode located in a healthysubject’s extensor digitorum brevis. (B) Endplate spikes with atriphasic configuration recorded from a healthy subject’s extensordigitorum brevis.

FIGURE 2. A single muscle fiber is depicted with three recordingelectrodes (E-1A), (E-1B), and (E-1C). E-1C produces action po-tential blockade through a “sealed end” effect. An action potentialis generated at the endplate zone (quadrupole: + − − +). (A–H)The relationship of the electrode and various portions of the qua-drupole determines what each recording electrode detects withrespect to waveform configuration. (From Dumitru et al.,27 withpermission.)

Table 1. Differentiating normal and pathologic single musclefiber discharges.*

Fibrillations/PSWs EPS

Morphology Biphasic, initiallynegative

Biphasic, initiallynegative

Triphasic, initiallypositive

Triphasic, initiallypositive

Biphasic, initiallypositive (PSW)

Biphasic, initiallypositive (PSW)

Complex ComplexFiring rate Regular IrregularDischarge

frequency∼7.4 HZ (up to 15

HZ)∼19 HZ (20–50 HZ

or more)

EPS, endplate spikes. PSW, positive sharp waves.*“Complex” refers to spontaneous discharges with configurations thatappear to be a summated result of more than a single spontaneousdischarge.


brillation potentials when multiple potentials are dis-charging simultaneously. The primary point is thattriphasic endplate spikes are common and should beconsidered a typical appearance for endplatespikes.27

“Atypical” Biphasic/Monophasic Endplate SpikeConfiguration. It is also very common to observeendplate spikes that are biphasic or monophasic ini-tially positive, both of which may resemble positivesharp waves. Prior to explaining the configuration ofthese waveforms, it is necessary to first consider twodifferent types of possible needle interactions withthe muscle fiber. As noted above, the needle elec-trode has a certain mass associated with its physicalpresence and acts to plow muscle tissue out of its wayduring insertion. This “mass effect” has been postu-lated to interact with muscle in one of three ways.22

First, the electrode may either fail to compress oronly slightly compress the muscle fiber, therebyminimally impeding action potential propagation.In this instance, one would anticipate normal actionpotential propagation associated with a triphasicwaveform (Fig. 2A–H; E-1B). However, the needleelectrode may also adversely affect action potentialpropagation in one of two ways. First, the electrodemay completely compress the muscle fiber, preclud-ing action potential propagation past the electrode(“sealed end” effect). Second, a “compressed end”effect may occur; following crush or compression oftissue, the membrane retains no functional sodium

channels and, therefore, can only sustain an ap-proaching passive current flow, but not an active cur-rent flow.45

With the “sealed end” effect, the action poten-tial’s leading dipole encounters the affected portionof muscle tissue, it begins to dissipate because of thelack of any current source to “feed” its current sink(Fig. 4E,F). This LD dissipation continues until it iscompletely gone. The TD in turn encounters thefiber’s sealed end and also begins to dissipate. Aswith the LD, the TD continues to “collapse” on itselfat the tissue’s electrical termination until it too iscompletely gone.

With the “compressed end” effect, passive intra-cellular-to-extracellular local current for the LD cancontinue to “feed” the LD’s negative current sink.That is, there is some finite length of muscle intowhich the negative sink of an action potential cannotpenetrate because no functional sodium channelsare present, but some degree of forward-moving cur-rent flow by the LD’s local circuit current is permit-ted. Therefore, as the action potential’s LD first en-counters the transition zone between normal andcompressed tissue, the positive portion of the LDenters the compressed region of membrane (Fig.4A–D). The result of this process is that the actionpotential stops propagating at the compressed zoneinitiation, but unlike the sealed end termination, theaction potential’s LD and then TD do not sequen-tially dissipate. Rather, the LD’s positive source cur-

FIGURE 4. (A–D) A schematic representation of an action potential (triangle) with its LD and TD propagating toward a compressedtermination (double dashed line). Both the LD and TD are preserved throughout action potential dissipation. (E–H) An action potential(triangle) encounters a “sealed end” (vertical dashed line). In this case, first the LD then TD dissipate in turn because there is nomembrane to the right of the dashed line to sustain the action potential.


rent continues to “feed” the action potential’s nega-tive current sink. As those sodium channelsimmediately adjacent to the compressed zone beginto inactivate, the entire action potential dissipateswith both the LD and TD intact until all of the so-dium channels are inactivated and the cell is com-pletely repolarized.

When a recording electrode is inserted intomuscle tissue with its shaft irritating a terminal nervefiber and the active recording surface is several hun-dred microns from the endplate, a particular wave-form is recorded if the electrode produces a sealedend termination effect (Fig. 2; E-1C). An initial posi-tive deflection is recorded by the electrode as theaction potential’s LD approaches its location. Thispositivity increases until the LD encounters thesealed end termination. The LD then begins to dis-sipate since further action potential propagation isprecluded and there is no membrane from which todraw a source current. The dissipating LD results ina reduction in the waveform’s initial positive deflec-tion. Following dissipation of the LD, the negativepole of the TD is now adjacent to the electrode,generating a negative deflection. The magnitude ofthis negative deflection is not as great as the initialpositive deflection because the TD is much moretemporally dispersed than the LD in accordancewith the respective times of depolarization (∼1 ms)and repolarization (∼4 ms). This temporal differ-ence also accounts for the longer duration negative,compared to positive, spike. Therefore, the compar-atively smaller negative spike also begins to dissipateas the membrane repolarizes and eventually settlesback to baseline. The appearance of a waveform en-countering a sealed end termination is similar to apositive sharp wave in that it displays an initial posi-tive deflection and longer duration but lower ampli-tude negative phase, i.e., it is biphasic and initiallypositive. This waveform may appear similar to a posi-tive sharp wave, but its firing rate is identical to thatof the more prototypical or triphasic endplate spike(Fig. 5A).

When the needle electrode is inserted just as de-scribed but produces a compressed termination, theelectrode detects an initial positive deflection asso-ciated with the approaching action potential’s LD(Fig. 6A–H; E-1C). The positive deflection increasesin magnitude the closer the LD approaches. At somepoint the LD and thus the entire action potentialceases to propagate when the compressed zone isencountered, as there are no longer any functionalsodium channels. The LD is still present because it is“fed” by the LD’s local circuit current. However, theinitiation of sodium inactivation begins to shut down

the negative sink. Because there is a declining avail-ability for sodium ions to enter the membrane, theLD and TD begin to collapse in on themselves. Thepositive deflection recorded by the electrode alsobegins to decline in magnitude. The process of LD/

FIGURE 6. (A–H) Similar situation as described in Figure 2 ex-cept the termination effect is that of a compressed end not asealed end. Note the LD and TD do not dissipate in turn, butdissipate simultaneously (E-1C). This precludes the TD’s terminalnegative sink from being detected by the electrode. The endresult is a monophasic positive waveform. (From Dumitru D:Muscle-generated spontaneous activity. Lecture syllabus, Ameri-can Association of Electrodiagnostic Medicine, 2000, with per-mission.)

FIGURE 5. (A) Biphasic, initially positive endplate spikes and (B)monophasic positive endplate spikes recorded from a healthysubject’s extensor digitorum brevis with a monopolar electrode.Note the documentation of two different irregularly firing endplatespikes (arrows) that resemble a positive sharp wave.


TD collapse continues until all of the sodium chan-nels are inactivated. The final waveform recorded bythe electrode is a monophasic positive waveform(Fig. 6A–H; E-1C). Although this waveform may alsobe mistaken for a positive sharp wave, its firing rateis identical to that of the more prototypical appear-ing endplate spike (Fig. 5B).

As can be easily observed, endplate spikes havethe potential for many different configurations:1) biphasic, initially negative; 2) triphasic, initiallypositive; 3) biphasic, initially positive; and 4) mono-phasic positive. The last three waveforms may be mis-taken for pathologic fibrillation potentials and posi-tive sharp waves if great care is not exercised inassessing the waveform’s firing rate (Table 2). Addi-tionally, it is highly likely that several of these wave-forms from different muscle fibers may overlap atthe electrode recording site so as to be summatedelectrically by the electrode. The net result are com-plex appearing endplate spikes with many differentconfigurations.27,79 It is possible that a number ofreports describing abnormal spontaneous activity inhealthy persons for the intrinsic foot and paraspinalmuscles may, in fact, be detecting, at least in part,endplate spikes with morphologies similar to abnor-mal potentials.18,33,50,78 This is possible because theendplate zone in intrinsic foot and paraspinalmuscles is more likely to be encountered by an ex-ploring electrode than in larger limb muscles, be-cause the endplate zone is a larger percentage of themuscle’s length.11,74 Further, the endplate zone ofthe intrinsic foot muscles are not well known and“blind” insertions into the paraspinal region cannotdiscern the endplate region, thereby increasing thelikelihood that this portion of the muscle may beexplored.

MOTOR UNIT ACTION POTENTIAL

The motor unit action potential (MUAP) can bethought of as the summation of the individual po-tentials of all the muscle fibers comprising a singlemotor unit. However, it is also necessary to considerthe relationship the single muscle fiber intracellularaction potential (IAP) has to the MUAP from theperspective of near-field and far-field components.For the present purposes, a near-field describes aregion where a generator source’s associated voltagechanges rapidly with small changes in the recordingelectrode’s position.73 A far-field is that portion ofthe generator’s voltage distribution that changeslittle despite large alterations in the recording elec-trode’s position.

A single muscle fiber’s IAP has already been de-scribed as monophasic positive. However, its termi-nal repolarization phase has been documented to

approach 30 ms.55 This long terminal repolarizationarises from the combined repolarization of the trans-verse tubule system.56 If it is assumed that a muscleIAP conducting at 3.7 m/s has a depolarization andrepolarization phase approximating 1 ms and 30 ms,respectively, the spatial distribution of these twophases encompasses a membrane length of 3.7 mm(LD) and 111 mm (TD). A simulated muscle fiber100 mm in length can be used to explain a MUAP’sconfiguration.

Three electrodes can be positioned along thismuscle fiber at the endplate zone (Fig. 7; E-1A: 0mm), midway between the endplate and fiber’s ter-mination (Fig. 7; E-1B: 25 mm), and 5 mm beyondthis previous electrode (Fig. 7; E-1C: 30 mm.)25 Anelectrode positioned at the endplate region will rec-ord a biphasic, initially negative waveform, whereaselectrodes located about the fiber’s middle will rec-ord a triphasic, initially positive waveform (Fig. 7).

At the instant before the IAP’s LD encounters themusculotendinous junction, the above noted threeelectrodes describe a declining magnitude positivephase (Fig. 7D). This portion of the waveform isdiminishing in amplitude because the IAP’s extracel-lularly associated near-field distribution is decliningwith repolarization and movement away from theelectrodes. However, as soon as the IAP’s LD beginsto encounter the fiber’s musculotendinous junction,it not only ceases to propagate, but also diminishesin length and, hence, dissipates. Since the IAP’s LDmoment no longer balances its TD moment, an im-balance is created between the two dipoles. When-ever a dipolar imbalance is generated, an associatednet dipole arises from this situation (Fig. 7E).73 If adipole is located in a cylindrical volume conductorsuch as a limb, it generates a far-field potential. Themagnitude of this far-field potential is maximizedwhen the LD has completely dissipated leaving onlythe trailing dipole (Fig. 7F). All of the three elec-trodes in this example will detect the initiation ofthis far-field potential as a small positive deflection inthe recorded waveform’s terminal return to baseline(Fig. 7; E-1A, E-1B, E-1C). The polarity of this far-field potential is positive only because the recordingelectrodes are located in the positive region of thenet dipole whereas the reference electrode is posi-tioned far from the active electrode. As the IAP’s TDbegins to dissipate, the far-field potential begins todecline (Fig. 7G). This dissipation will require ap-proximately 30 ms since the TD is associated with theIAP’s repolarization phase. Therefore, the singlemuscle fiber’s waveform duration in this examplewill approach 30 ms.

Summating the potentials of all of the musclefibers within a motor unit should result in a MUAP


with a configuration similar to that of a single musclefiber action potential. Utilizing the above informa-tion generates simulated MUAPs with configurationswell-representative of MUAPs recorded clinicallywith a monopolar needle and averaging many re-sponses to improve the signal-to-noise ratio (Fig. 8).Recording at different locations along the musclefiber reveals that the MUAP’s onset is the same irre-spective of recording location. This is to be antici-pated since the MUAP’s onset is dependent uponendplate depolarization and not electrode location.Averaging many MUAP responses permits its onsetto be appreciated (Fig. 8). However, the main spikeof the MUAP is delayed commensurate with how farthe electrode is from the endplate region (Fig. 8A–D). This delay occurs because the MUAP’s mainnegative spike is generated by the IAP’s summatednegative sinks’ arrival at the electrode’s location. Fol-lowing the MUAP’s negative spike is the terminalrepolarization or positive phase. An additional posi-tive phase contained within this terminal repolariza-tion phase can be easily appreciated (Fig. 8A–D) andconforms to the previously described positive far-field potential (Fig. 7).

The various components of a MUAP can now befully appreciated and result in a distinction betweenthe MUAP’s clinical and physiologic duration.23,24,63

A MUAP’s physiologic duration is the temporal do-main between its initial departure from baseline andthe eventual return of the far-field potential back tobaseline. This may exceed 30 ms and consists of anear-field and far-field component. The near-fieldcomponent is from initial baseline departure to ini-tiation of the far-field potential (Fig. 8). The MUAP’sfar-field component extends from far-field initiationto its baseline return. MUAP near-fields are indepen-dent of recording location along the muscle fiber,but directly dependent on muscle fiber length. Thelonger the muscle fiber, the longer the MUAP’snear-field duration because there is more muscle fi-ber for IAP propagation. The MUAP’s far-field com-ponent is independent of fiber length, but dependson the IAP’s repolarization phase.

A MUAP’s clinical duration primarily consists ofa portion of its near-field component only and typi-cally approximates 10 ms in normal persons. Com-paratively reduced amplifier gains and low signal-to-noise ratios results in only a portion of the MUAPbeing detected by visual inspection in most cases.Slope-amplitude criteria used in automatic MUAPanalysis truncates the MUAP’s initial and terminalportions, extracting a MUAP with durations similarto those obtained through visual inspection meth-ods. Increasing (neurogenic disorders) or decreas-

FIGURE 7. Half of a 100 mm simulated single muscle fiber is depicted with an electrode positioned at the endplate zone (E-1A: 0 mm),midway between the endplate and musculotendinous junction (E-1B: 25 mm), and 5 mm beyond this point (E-1C: 30 mm). (A–D) The IAPis represented by a quadrupole (+ − − +) which initiates at the endplate zone and terminates at the musculotendinous junction (50 mm).(E–H) When the IAP’s LD encounters the fiber’s termination, it begins to dissipate, leading to a dipolar imbalance between the leadingand trailing dipole with a superimposed net dipole {+ −} thereby generating a far-field potential. (From Dumitru et al.,25 with permission.)


ing (myogenic disorders) the number of muscle fi-bers per motor unit will either increase or decreasethe magnitude of all portions of the MUAP, permit-ting visual inspection and computer-assisted meth-ods of analysis to conclude there is a respective in-crease or decrease in the MUAP’s clinical duration.It is likely that the MUAP’s physiologic duration hasnot dramatically changed in various disorders, butrather its clinical duration has changed dependingupon whether its initial and terminal near-field com-ponents can be detected above the backgroundnoise.

COMPOUND MUSCLE ACTION POTENTIAL

The preceding MUAP information can be used toexplain less-commonly appreciated aspects of thecompound muscle action potential (CMAP). TheCMAP derived from the abductor pollicis brevis(APB) and abductor digiti minimi (ADM) is used todiscuss near-field and far-field muscle components.

A biphasic initially negative CMAP is typically re-corded from the APB following median nerve acti-vation (Fig. 9A). As noted above, this potential’s on-set is negative because the recording electrode ispurposefully positioned over the muscle’s endplatezone. The CMAP’s terminal positive phase is to beexpected because this represents the fibers’ repolar-

ization phase (Fig. 9A; P1). However, this positivephase is in large part due to the summated far-fieldpotentials generated from the combined IAPs en-countering the musculotendinous junction. Slowingthe recording sweep speed reveals that the APB’sterminal positive phase approaches 60 ms (Fig. 9B).This long terminal phase results from the summatedeffect of the APB’s far-field potential and F-wavecomponents.

The concept of near-field and far-field interac-tions is perhaps best exemplified by the CMAP ofADM following ulnar nerve stimulation. A CMAP de-rived from the ADM with an active (E-1) electrodeon the motor point and the reference (E-2) elec-trode on the fifth digit typically demonstrates a bi-lobed negative spike (Fig. 9C; N1 and N2). If the E-1electrode is repositioned on the medial epicondyle,a large triphasic, initially positive, far-field potentialis recorded. This is a far-field potential because bothelectrodes are relatively far from the ADM (Fig. 9D).It can be seen that this far-field potential’s negativespike coincides with the second negative spike con-tained within the usually recorded CMAP of theADM (Fig. 9C,D). Additionally, the ADM’s large ter-minal positive phase is clearly a far-field potential(Fig. 9C; P1 and Fig. 9D; P2). Thus, the CMAP de-rived from the ADM under routine conditions is a

FIGURE 8. (A) A simulated MUAP recorded with a monopolar montage revealing a near-field component (region between the first twovertical dashed lines) and a far-field component (segment between second and third vertical dashed lines). (B) Same situation as depictedin (A) except the recording location is about 5 mm further along the fiber. Note that the MUAPs in (A) and (B) have the same onset butthe negative spike is time shifted slightly to the right in (B). Further, the near-field and far-field components are of the same respectiveduration. (C–D) Two MUAPs recorded with a monopolar needle from a biceps brachii muscle of a healthy individual showing the samefindings predicted by the simulation. (From Dumitru et al.,25 with permission.)


combination of near-field potential from the ADMand far-field potentials from additional ulnar-innervated intrinsic hand muscles.47,58 Finally, a slowsweep-speed following ulnar nerve stimulation whilerecording from the ADM also demonstrates a totalwaveform duration approaching 60 ms for reasonsdescribed above for the APB (Fig. 9E).

MYOTONIC DISCHARGES

Disorders generating myotonic discharges resultfrom either an inherited or acquired abnormality ofeither the sodium or chloride channel and are there-fore designated as channelopathies.5

Sodium Channel Mutations. Different mutations ofthe human adult skeletal muscle sodium channel’s(hSkM1; gene SCN4A chromosome 17q23.1-25.3)a-subunit have been recognized in families with po-tassium aggravated myotonia (PAM), paramyotoniacongenita (PMC), and hyperkalemic periodic paraly-

sis (HPP).12,67 The sodium ions traverse the sodiumchannel without difficulty, but the primary defectrelates to the voltage-dependent gating characteris-tics of the channel, i.e., the mechanics of its openingand closing.53 The major problem identified withthe sodium channel is an alteration of fast inactiva-tion.8,36,37,60 Following depolarization and, hence,sodium channel opening by activation, the normalsodium ion channel rapidly enters an inactivatedstate through the process of fast inactivation and willnot open again until the transmembrane voltage hasbeen restored to the polarized state approaching theRMP. The activation/inactivation cycle is the basis ofthe refractory and relative refractory periods. Thecritical process of fast inactivation has two importantfunctions: limitation of the action potential’s dura-tion, and initiation of membrane repolarization.70 Inmutant sodium channels, the rate of inactivation isslowed, thereby increasing the action potential’s du-ration and decreasing the contribution to mem-brane repolarization. Further, some mutant sodiumchannels in the above disorders also display a fasterrecovery from inactivation. This increases the prob-ability of opening prior to full membrane polariza-tion and results in an uncoupling of the inactivationprocess from voltage dependence, and bursting ofthe sodium channels where multiple openings andclosings occur during the expected inactivation timeframe.4,8 All of these abnormalities result in a smallbut steady inwardly directed sodium current followingan action potential that further depolarizes the cell ina progressive cascade. Only a small number of mutantchannels (∼2%) need to be present in the membraneto partially depolarize the cell and predispose it to re-petitive discharges by also affecting the wild type chan-nel functioning.13,14 If the percent of abnormal func-tioning sodium channels increases slightly (∼3% ormore), a more depolarized transmembrane potentialwill ensue and result in muscle fiber paralysis frominactivation of too many sodium channels.

Chloride Channel Mutations. Mutations of the chlo-ride channel gene (CIC-1; gene CLCN1 chromosome7q35) can also result in myotonic discharges whichare primarily observed in two inherited disorders: 1)autosomal-dominant Thomsen’s myotonia conge-nita, and 2) autosomal-recessive Becker myotoniacongenita.61 The primary defect in these disorders isa reduction in the ability of the chloride ion to passthrough the sarcolemmal membrane, i.e., a low chlo-ride ion conductance.

Other Disorders. Myotonic discharges also occur ina number of disorders in which the exact mechanismof sarcolemmal membrane instability has yet to be

FIGURE 9. (A) Biphasic initially negative CMAP obtained fromthe APB with an active electrode on the muscle’s motor point anda reference on the distal thumb. (B) Similar recording montage asin (A), however, 30 stimuli were averaged and the sweep speedwas slowed to 10 ms/div. (C) Biphasic initially negative CMAPfrom the ADM with a bilobed negative spike. (D) Relocating theactive electrode from the ADM to the lateral epicondyle reveals atriphasic initially positive far-field potential. (E) Same recording asthat in (C), but with a sweep speed of 10 ms/div. Note: N1 and N2refers to the first and second negative peaks while P1–P2 refer tothe first through second positive peaks. The designation “F” de-marcates the CMAP’s associated F wave.


defined. A few reports suggest that patients withmyotonic dystrophy may have sodium channel ab-normalities with a defective inactivation system40 aswell as possible potassium ion conductance abnor-malities.48,59 Also, a report has suggested that similarto denervated muscle, myotonic dystrophy may pre-dispose the muscle to develop apamin-sensitive cal-cium-activated potassium channels which may playsome role in the repetitive discharges of myotonicmuscle.6 It also appears that late sodium channelopening may occur in chondrodystrophic myotonia(Schwartz–Jampel syndrome).52 The exact mecha-nism of myotonic discharge remains to be elucidatedfor proximal myotonic myopathies (PROMM).62 It ispossible to acquire myotonic discharges by consump-tion of monocarboxylic aromatic acids (e.g., anthra-cene-9-carboxylic acid) and the herbicide 2,4-D (2,4-dichlorphenoxyacetic acid) secondary to a drug-induced reduction in chloride conductance.10

Further research will eventually reveal the underly-ing channel abnormality responsible for these disor-ders.

Intracellular Potentials. Resting Membrane Potential.The resting muscle membrane potential is normal inboth the sodium and chloride channelopathies thatproduce myotonic discharges.70 A normal or slightreduction in the RMP by about 10 mV may be foundin some patients with myotonic dystrophy.32,70

Repetitive Spontaneous Action Potential Genera-tion. The primary feature distinguishing myotonicdischarges is the repetitive firing in a so-called wax-ing and waning manner, with the membrane even-tually returning to a quiescent stage. In order tomore fully appreciate why muscle membranes dis-play myotonic discharges, it is necessary to considerthe transverse tubule system. The transverse tubules(T-system) are channels lined with sarcolemmalmembrane that traverse the muscle fiber so that theaction potential can penetrate into the muscle fiber.This action potential penetration facilitates efficientexcitation-contraction coupling. The T-system formsa very small cylinder of extracellular fluid in conti-nuity with the extracellular space, but within the con-fines of the muscle fiber. It is this small cylindricalspace that becomes crucial for the eventual genera-tion of repetitive discharges when defective ionchannels are present.

Normal Sodium and Chloride Channels (HealthyMuscle Fibers). When an action potential is propa-gating along the sarcolemma and enters a T-tubule,the sodium channels within the T-tubule membranerespond to the depolarizing impulse by activating(opening) in a positive feed-back manner when the

membrane’s threshold voltage is achieved (sodiumactivation). Within a millisecond of opening, sodiuminactivation occurs, terminating further sodium ionentry, limiting the action potential’s duration, andinitiating the repolarization process. Potassium acti-vation lags slightly behind sodium activation andpermits potassium ions to flow “down” their concen-tration (high intracellular to low extracellular) andvoltage (relative intracellular positivity during the ac-tion potential) gradients to further facilitate repolar-ization. However, the small T-tubule volume com-pared to the intracellular space only permitspotassium to accumulate for a very short time for asingle action potential. The T-tubule potassium ionconcentration then reaches a level that acts to in-hibit further potassium exiting the cell, which inturn fails to accomplish repolarization to the RMP of−80 mV. This is quite unlike the surface sarcolemma,where potassium ions can quickly diffuse into theextracellular space so that the relative intracellularpotassium ion concentration remains comparativelylarger. In normal muscle, each action potential re-sults in a 1 mV reduction in the RMP value com-pared to the previous RMP and requires about 400ms to dissipate without help from another process.12

This reduction summates with each successive dis-charge if the interdischarge interval is less than 400ms. The RMP of −80 mV can be restored by thechloride ion flowing down its voltage (intracellularpositivity during depolarization) and concentration(high extracellular to low intracellular) gradients.Therefore, full repolarization can only occur if thesethree mechanisms function properly: 1) sodium in-activation to stop sodium ion entry, 2) potassiumactivation to begin to repolarize the membrane, and3) chloride ion entry to accomplish full reestablish-ment of the RMP. A failure in any one of these pro-cesses not only results in a propensity for the mem-brane to fail to reestablish the original RMP, but alsopermits the cell’s transmembrane voltage to achievea new steady-state value that may be above the mem-brane’s threshold. Should this occur, when the so-dium channels recover from the inactivation pro-cess, they will again open to initiate another actionpotential because the “new” membrane potentialeventually becomes suprathreshold.

The validity of the above description of actionpotential initiation has been established in animalmodels.1,2,15,17 Placing healthy muscle tissue in bathsfree of chloride ions or using sea anemone toxins toimpair sodium inactivation both result in myotonic-like discharges. However, removing the T-tubule sys-tem from these same preparations abolished the re-petitive discharges, thereby verifying the need for an


intact T-system in order to produce myotonic dis-charges.

Defective Chloride Channels. In a muscle fiberwith defective chloride ion channels that cannotconduct the ion to a sufficient degree across thesarcolemma in either the surface or T-systems, re-petitive discharges may occur. When an action po-tential propagates into the T-system, the sodiumchannels activate normally, resulting in membranedepolarization followed by sodium inactivation andthe initiation of membrane repolarization. Potas-sium exits the cell in an attempt to repolarize themembrane but achieves this to a somewhat limitedextent secondary to a quickly rising T-system (extra-cellular) potassium ion concentration.13,71 As a re-sult, the anticipated RMP of −80 mV is only partiallyreestablished; perhaps to −70 mV. It is necessary forchloride ions to flow into the cell to further repolar-ize the cell, but reduced chloride conductance sec-ondary to defective channels precludes this fromhappening. The end result is a RMP with a value thatis more positive than normal but likely not above themembrane’s threshold.

If several action potentials propagate into the T-system, and each succeeding action potential raisesthe RMP to a progressively more positive level, atsome point, the RMP will end up above the voltagethreshold at which sodium channels open. The T-tubule membrane then spontaneously depolarizesand produces action potentials that propagate outfrom it onto the membrane’s surface. The cycle maybe recurring and produce myotonic discharges.Each subsequent depolarization, however, results ina smaller difference between the ever more positiveRMP and the maximum positive peak action poten-tial voltage of about +40 mV. Therefore, each actionpotential will be smaller in amplitude because theresting membrane potential is progressively lessnegative, and the action potential’s peak is progres-sively less positive because more and more wild-typesodium channels are left inactivated. The action po-tential rate may also increase to the possible rate-limiting step of how long it takes the channels tocycle between sodium activation and inactivationback to activation again. The extracellular action po-tential will then slow its firing rate and decline inmagnitude during the myotonic discharge. The myo-tonic discharge will eventually cease when the cell’sdefective repolarization process fails to reduce thetransmembrane potential below that of the approxi-mate sodium equilibrium potential (∼+67 mV). It isthe defective chloride conductance combining withthe constraints of the T-system that results in therepetitive discharges observed in chloride chan-

nelopathies and the eventual dysfunction of sodiumchannels secondary to a depolarized membrane.

Defective Sodium Channels. A small percent ofdefective sodium channels may be present, with themajority being normal such that channel activationfunctions normally, but channel inactivation is al-tered for those mutant channels.14,34,54 This alter-ation consists of both a slowing of inactivation so thatthe sodium ion channel stays open longer, and afaster than normal recovery from the inactivatedstate. An incomplete persistent inactivation may alsobe present: the sodium channel initially inactivates,but then reopens spontaneously during the antici-pated inactivation period, i.e., its voltage depen-dence is uncoupled.

When an action potential enters the T-system,therefore, the cell is depolarized as expected. So-dium inactivation, however, is delayed and a sodiumcurrent flows for a longer time than normal. Potas-sium attempts to repolarize the membrane by exit-ing the cell to enter the T-system confines. This pro-cess by itself cannot fully reestablish the RMP.Chloride conductance is assumed to be normal andflows into the cell down its voltage and concentra-tion gradients, attempting to restore the RMP. Thetransmembrane voltage may be restored to a valuebelow the membrane’s threshold, but the rapid re-covery from sodium inactivation and possible con-tinued sodium current bursting acts to depolarizethe membrane again prior to reestablishment of theRMP at its normal value of −80 mV. This process nowrepeats since the inwardly directed sodium currentsimply keeps reinitiating an action potential thatpropagates out of the T-system and along the surfacesarcolemma. As with defective chloride conduc-tance, the subsequent action potentials decline inmagnitude, and increase or decrease in firing rateuntil the membrane is no longer capable of sustain-ing an action potential. Eventually the membranerecovers to repeat the process.

Myotonic Discharge Configuration. As noted above,myotonic muscle fibers with abnormal channels areinnervated and for the most part have a normalRMP. Therefore, one can anticipate a monophasicpositive intracellular action potential as observed fornormal muscle fibers. As a result, the single musclefiber waveform configurations should appear thesame as previously described for innervated musclefibers with normal functioning ion channels. Thereis little in the way of information concerning thedetails of myotonic discharge morphologies.22 Per-sonal observations of myotonic discharges recordedat relatively fast sweep speeds reveal waveforms with


configurations consistent with that discussed above,i.e., biphasic initially negative (similar to an endplatespike), triphasic initially positive, and biphasic ini-tially positive (sealed end potential), as well as mono-phasic positive (compressed end potential). TheL/TD model applies equally well for healthy andmyotonic discharges.

Careful needle insertion into a patient’s musclewith myotonia can produce a single series of myo-tonic discharges (Fig. 10). It is reasonable to assumethat a single muscle fiber is responsible for theserepetitive discharges. If one accepts this premise,then the truly remarkable finding is the frequentlyobserved variation of the waveforms within this dis-charge train. The muscle fiber, needle electrode,and action potential are all constant yet a markedtransformation of the different waveform configura-tions may occur throughout the discharge (Fig. 10).It is true that the intracellular action potential isdeclining in magnitude as revealed by intracellularrecordings, but its morphology does not change andhence neither should its extracellular counterpart.

Application of the L/TD model can be used tobetter appreciate how a single muscle fiber can dis-play such an array of waveforms during the course ofa single discharge. Although the muscle fiber candisplay any sequence of waveform morphologies de-pending upon the conditions present between therecording electrode and muscle fiber, a single ex-ample suffices to gain insight into the overall pro-cess.

The first discharge observed in Figure 10 is bi-phasic and initially negative. This suggests that the

needle electrode initiated the discharge in the im-mediate vicinity of its recording tip. However, theterminal positive phase is rather large compared tothe initial negative spike, suggesting that a com-pressed end effect may simultaneously be presentbecause a negative phase does not follow the largepositive deflection. After the first discharge, thewaveform configuration changes to that of a tripha-sic and initially positive waveform in which the initialpositive deflection is small compared to the negativespike.27 The terminal positive phase is now smallerthan in the first discharge. These findings suggestthat the generator site for the waveform shifted a fewhundred microns from the needle tip (or that theneedle moved slightly) so that the induced actionpotential now propagated toward the recording elec-trode and then possibly blocked. Shortly thereafter,the waveform morphology changes to that of a bi-phasic and initially negative waveform with a promi-nent terminal positive phase (Fig. 10). This suggeststhe generator site has again shifted to coincide withthe needle’s recording tip with a coincident terminalcompressed end effect. The waveform then gradu-ally alters its configuration from a biphasic and ini-tially negative potential to a monophasic positivewaveform. In this case, it appears the site of actionpotential initiation has progressively shifted awayfrom the electrode while continuing to block at theelectrode tip secondary to a compressed end effectuntil such time that the action potential ceased todischarge. The reason that the presumed site ofaction potential generation shifts is unclear and re-quires further investigation. It is also possible to ob-serve myotonic potentials that maintain a morphol-ogy similar to that of a positive sharp wave (sealedend blockade), or triphasic (no needle inducedblockade) throughout their discharge train. Morecommonly, however, the myotonic runs appearrather complex because the needle electrode hasinduced spontaneous discharges in multiple fiberswith superimposition of many single muscle fiberwaveforms.

DENERVATED MUSCLE TISSUE

Intracellular Potentials. Resting Membrane Potential.The RMP of a muscle fiber becomes less negative byapproximately 15 mV within about 30 h of neuralloss, i.e., denervation.69,76 This alteration in the RMPresults from an increase in sodium permeability andreduction in potassium permeability.50 Additionally,a new type of sodium channel is synthesized that issignificantly more resistant to the effects of tetrodo-toxin (TTX; a sodium channel blocker from thepuffer fish).77 The new sodium channels appear to

FIGURE 10. Continuous recording (from top to bottom) from amonopolar needle electrode inserted into the first dorsal interos-seous muscle of a patient with myotonic dystrophy. Note themyotonic run of potentials with a constantly changing waveformconfiguration. (From Dumitru D: Muscle-generated spontaneousactivity. Lecture syllabus, American Association of Electrodiag-nostic Medicine, 2000, with permission.)


have altered kinetics with respect to demonstratinghalf the recovery time for fast inactivation comparedto sodium channels in innervated muscle. A newtype of potassium channel is also synthesized follow-ing denervation and is apamin- (bee venom deriva-tive) sensitive and calcium-activated.5,42,72

Repetitive Spontaneous Action Potential Genera-tion. Locating a microelectrode into a muscle fiberthat has been denervated for several days reveals anumber of interesting findings. The RMP is not onlyless negative than normal, but it also displays spon-taneous biphasic oscillations of progressively increas-ing magnitude.75 The progressive increase in magni-tude for these membrane oscillations continues untilthe membrane threshold level of approximately −65mV is reached.

The action potential depolarizes toward the so-dium equilibrium potential (+67 mV), overshootsthe zero level by about +20 mV, and begins to repo-larize secondary to sodium inactivation and potas-sium activation assisted by chloride flowing into thecell. The end result of this process is similar to thatobserved in innervated muscle. However, a very im-portant difference exists between the action poten-tials of denervated and innervated muscle. As previ-ously mentioned, there are newly synthesizedpotassium channels and these produce a long-duration hyperpolarization of the intracellular ac-tion potential compared to normal tissue.7,68,76 Thishyperpolarization may last up to 100 ms or more.The newly synthesized sodium channels recoverfrom inactivation faster than their “normal” counter-parts. This along with the membrane’s lower thresh-old level permits the sodium channels to respond toa depolarizing current sooner than anticipated forinnervated tissue. The terminal portion or recoveryphase of the outward directed potassium current ineffect constitutes a depolarizing current which servesto activate the now recovered sodium channels. An-other way of stating this concept is that, followingdenervation, not only is the denervated membrane’sRMP less negative, but the membrane’s thresholdvalue is actually more negative by about 9 mV,thereby bringing closer together the resting mem-brane voltage and threshold voltage for membranedepolarization.75 The combination of the mem-brane’s lower threshold value and relative “depolar-izing” afterpotential act to reinitiate a second depo-larization, which, in turn, activates anotherpotential, and so on. The end result is a repetitivefiring of the membrane with an interdischarge inter-val dependent upon the duration of the hyperpolar-ization phase and when it again reaches the mem-brane’s threshold value.

L/TD Model of Denervated Action Potentials. Asnoted above, the monophasic positive intracellularaction potential for healthy muscle tissue whenviewed extracellularly can be conceptualized as aquadrupole with depolarization represented by theLD and repolarization by the TD (Fig. 11A–C). How-ever, the intracellular action potential for denervat-ed muscle tissue is biphasic by virtue of the terminalhyperpolarization phase. The initial positive phasemay be considered to represent membrane depolar-ization and repolarization back to the RMP. In thismanner, the denervated intracellular action poten-tial can be modeled as an octapole with a leadingquadrupole and a trailing quadrupole of reversedpolarity because of the trailing hyperpolarization(Fig. 11D–K). The L/TD model can be used to helpexplain the morphology of fibrillation potentials re-corded at different locations along the muscle fiberas well as the configuration of positive sharp waves.

An important aspect of denervated muscle fibersis that there is only one configuration to the dener-vated muscle fiber’s intracellular action potential,i.e., biphasic positive–negative. Therefore, any at-tempt to explain the positive sharp wave must usethis action potential shape while at the same timeexplaining how a fibrillation potential with the sameaction potential can appear so different in durationand morphology. Combining the L/TD model andthe concept of the compressed end will permit anexplanation for both these waveforms, beginningwith the intracellular action potential.

A hypothetical muscle fiber may be considered,deprived of its innervation and with an action poten-tial beginning in the fiber’s middle and terminatingat a region of the fiber compressed by an exploringelectrode, i.e., a compressed end effect. Most fibril-lation potentials are believed to originate at themuscle fiber’s former endplate zone and propagateonto the fiber from there.43 At the former endplatezone, it may be assumed that a spontaneous mem-brane oscillation has reached threshold and initiatedan action potential. This action potential grows inmagnitude commensurate with the depolarizationachieving the membrane’s threshold level (Fig.11A,B; E-1A). If an electrode is located at this posi-tion, a waveform with an initial negative deflection isdetected, similar to the configuration of an endplatespike. Propagation of the action potential bidirec-tionally along the fiber can be expected, with themembrane’s repolarization (trailing dipoles for thetwo action potentials) becoming manifest at the elec-trode’s location. Hence, a positive waveform deflec-tion is then observed (Fig. 11C; E-1A). Continuedaction potential propagation would now permit the


action potential’s initial hyperpolarization phase tooccur in this region of the membrane (Fig. 11D–H;E-1A). The hyperpolarization phase occurs over avery long temporal domain, which means the cur-rent density associated with this portion of the actionpotential is relatively low. A way the extracellularwaveform is related to the intracellular waveform isoften described as its second derivative. That is, the“rate of rate of change” for the current at a particu-lar location. Since the hyperpolarization phase has acomparatively long time-course with respect to depo-larization, the magnitude of the extracellular wave-form associated with the portion of the action po-tential is negligible. The recorded waveform, simplysettles back to baseline even though there is a regionof hyperpolarization in the electrode’s vicinity. Thefinal waveform observed is biphasic and initiallynegative. This is exactly the type of fibrillation po-tential recorded from the former endplate zone of adenervated muscle fiber and appears identical to anendplate spike.

Consideration must also be given to the findingswhen the electrode is no longer located at themuscle fiber’s former endplate zone, but instead isrelocated halfway between the fiber’s middle and ter-mination so that an action potential can propagate

past it. Since the action potential was initiated at theformer endplate zone, it now travels toward the elec-trode so that the LD’s initial positivity can be de-tected (Fig. 11A–C; E-1B). Arrival of the leading qua-drupole’s negative sink produces a negative spike.Propagation of the action potential’s leading qua-drupole past the electrode generates a terminal posi-tive deflection. As with the endplate zone, the rate ofchange for the action potential’s terminal quadru-pole’s (hyperpolarization phase) voltage profile istoo slow to result in a detectable potential. The finalresult is a triphasic and initially positive potentialconsistent with a stereotypical fibrillation potential.

The findings will be influenced by whether theelectrode adversely affected the muscle fiber suchthat either a sealed end or compressed type of ter-mination is produced. If a sealed end effect is gen-erated by the electrode, a waveform with an initialpositive deflection and smaller terminal negativephase will be observed (Fig. 2; E-1C). This waveformhas an appearance quite similar to that for an inner-vated fiber because, as noted above, the denervatedaction potential’s hyperpolarization phase does notcontribute to the formation of an additional phasebecause of its slow rate of voltage change per unittime. These potentials appear similar to a positive

FIGURE 11. (A–L) Leading/trailing dipole explanation of a denervated intracellular action potential represented by an octapole (+ − − +,− + + −) propagating along a muscle fiber from left to right. Electrode’s are located at the fiber’s former endplate zone (E-1A), halfwaybetween the fiber’s middle and termination (E-1B), and at the fiber’s termination (E-1C). Note that only half the fiber is shown; the otherhalf projects to the left of the figure. (From Dumitru D: Muscle-generated spontaneous activity. Lecture syllabus, American Associationof Electrodiagnostic Medicine, 2000, with permission.)


sharp wave in that they are biphasic and initially posi-tive, but the terminal positive phase is comparativelybrief. Additionally, the firing rate of these waveformsis regular as would be anticipated for a typical fibril-lation potential.

If the electrode produces a compressed type ofinteraction with the muscle fiber, a completely dif-ferent effect is recorded with respect to the actionpotential’s hyperpolarization phase. The electrodedetects the approaching action potential’s leadingquadrupole’s positivity similar to the electrode thatpermits action potential propagation, thereby re-cording an initial positive deflection (Fig. 11E; E-1C).However, when the leading quadrupole’s LD en-counters the compressed membrane segment, itdoes not dissipate (Fig. 11F; E-1C). As for the com-pressed region of an innervated fiber, the leadingquadrupole’s LD and TD remain intact and dissipatewith membrane repolarization returning the wave-form’s initial positive deflection to baseline (Fig.11G; E-1C). When the trailing quadrupole’s LDreaches the compressed zone, it too does not dissi-pate but remains in place with its negativity “facing”the recording electrode. Further, the compressedzone increases the trailing quadrupole’s LD some-what permitting it to be detected by the electrode(Fig. 11H,I; E-1C). The net result is a waveform witha negative deflection. As with the leading quadru-pole, the trailing quadrupole now dissipates in placewith membrane depolarization back to the RMP(Fig. 11I–L; E-1C). A positive sharp wave is thus gen-erated and is postulated to represent a compressedtype of interaction between the electrode and mem-brane so that the denervated action potential’s hy-perpolarization phase is detected.

The above discussion highlights the differenttypes of waveforms that may be detected in dener-vated muscle. A fibrillation potential may appear bi-phasic and initially negative if it is recorded at its siteof initiation, biphasic but initially positive with ashort-duration terminal negative phase if detected bythe electrode that is generating a sealed end effect,or the more prototypical and triphasic initially posi-tive waveform secondary to action potential propa-gation past the electrode. A positive sharp wave canalso be observed if the fibrillating muscle’s actionpotential blocks at the site of the electrode second-ary to a compressed end effect induced by the elec-trode. Therefore, there are two fundamental wave-forms that can be recorded from denervated musclewith no electrode distortion (biphasic initially nega-tive and triphasic initially positive potentials), andtwo waveforms arising from needle distortion effects(biphasic initially positive with a short terminal nega-

tive phase, and biphasic initially positive with a rela-tively long terminal negative phase). There are alsocomplex-appearing potentials referred to as “hybrid”fibrillation potentials because they display configu-rations suggestive of both fibrillation potentials andpositive sharp waves.23 Additionally, when fibrilla-tion potentials transition to positive sharp waves orpositive sharp waves to fibrillation potentials, a num-ber of intermediate complex waveforms are usuallydisplayed.21 The explanation for these waveforms re-mains to be more fully developed.

CONCLUSION

Careful consideration of the intracellular action po-tential in both innervated and denervated musclefibers provides considerable insight into the type ofwaveform recorded by the electrodiagnostic instru-ment. The needle electrode is not merely a passivebystander but an active participant that influenceshow the waveform will appear. Application of thedeceptively simple leading/trailing dipole modelcan provide the clinician with considerable insightinto the underlying mechanism resulting in the par-ticular waveform observed. One cannot simply lookat a waveform and decide whether it arises from adenervated or innervated fiber. Rather, waveformconfiguration in combination with the discharge fre-quency must be considered. If a waveform persistsfor too short a time interval to accurately determineits discharge frequency, then no definitive conclu-sion can be derived from it. Continued research intovarious disorders should provide additional insightinto why waveforms appear as they do.

REFERENCES

1. Adrian RH, Bryant SH. On the repetitive discharge in myo-tonic muscle fibres. J Physiol 1974;240:505–515.

2. Adrian RH, Marshall MW. Action potentials recorded in nor-mal and myotonic muscle fibres. J Physiol 1976;258:125–143.

3. Barchi RL. Excitation and conduction in nerve. In: SummerAJ, editor. The physiology of peripheral nerve disease. Phila-delphia: Saunders; 1980. p 1–40.

4. Barchi RL. Ion channel mutations and diseases of skeletalmuscle. Neurobiol Dis 1997;4:254–264.

5. Barrett JN, Barrett EF, Dribin LB. Calcium-dependent slowpotassium conductance in rat skeletal myotubes. Dev Biol1981;82:258–266.

6. Behrens MIG, Jalil P, Serani A, Vergara F, Alvarez O. Possiblerole of apamin-sensitive K+ channels in myotonic dystrophy.Muscle Nerve 1994;17:1264–1270.

7. Belmar J, Eyzaguire C. Pacemaker site of fibrillation poten-tials in denervated mammalian muscle. J Neurophysiol 1966;29:425–441.

8. Bendahhou S, Cummins TR, Tawil R, Waxman SG, Ptacek LJ.Activation and inactivation of the voltage-gated sodium chan-nel: role of segment S5 revealed by a novel hyperkalaemicperiodic paralysis mutation. J Neurosci 1999;19:4762–4771.


9. Brazier MAB. Electrical activity of the nervous system. Lon-don: Pitman Medical; 1977. 248 p.

10. Bryant AH, Morales-Aguilera A. Chloride conductance in nor-mal and myotonic muscle fibres and the action of monocar-boxylic aromatic acids. J Physiol 1971;219:367–383.

11. Buchthal F, Rosenfalck P. Spontaneous electrical activity ofhuman muscle. Electroencephalogr Clin Neurophysiol 1966;20:321–336.

12. Cannon SC. From mutation to myotonia in sodium channeldisorders. Neuromuscul Disord 1997;7:241–249.

13. Cannon SC. Ion-channel defects and aberrant excitability inmyotonia and periodic paralysis. Trends Neurosci 1996;19:3–10.

14. Cannon SC. Sodium channel defects in myotonia and peri-odic paralysis. Annu Rev Neurosci 1996;19:141–164.

15. Cannon SC, Corey DP. Loss of Na+ channel inactivation byanemone toxin (ATXII) mimics the myotonic state in hyper-kalaemic periodic paralysis. J Physiol 1993;466:501–520.

16. Carpenter RHS. Neurophysiology. Baltimore: University ParkPress; 1984. 339 p.

17. Coonan JR, Lamb GD. Effect of transverse-tubular chlorideconductance on excitability in skinned skeletal muscle fibresof rat and toad. J Physiol 1998;509:551–564.

18. Date ES, Mar EY, Bugola MR, Teraoka JK. The prevalence oflumbar paraspinal spontaneous activity in asymptomatic sub-jects. Muscle Nerve 1996;19:350–354.

19. Dumitru D. Volume conduction: theory and application. InDumitru D, editor. Clinical electrophysiology. Philadelphia:Hanley & Belfus, 1989; p 665–681.

20. Dumitru D, Jewett DL. Far-field potentials. Muscle Nerve1993;16:237–254.

21. Dumitru D, King JC. Varied morphology of spontaneoussingle muscle fiber discharges. Am J Phys Med Rehabil 1998;77:128–139.

22. Dumitru D, King JC, McCarter RJM. Single muscle fiber dis-charge transformations: fibrillation potential to positive sharpwave. Muscle Nerve 1998;21:1759–1768.

23. Dumitru D, King JC, Nandedkar SD. Motor unit action po-tential duration recorded by monopolar and concentricneedle electrodes: physiologic implications. Am J Phys MedRehabil 1997;76:488–493.

24. Dumitru D, King JC, Nandedkar SD. Motor unit action po-tentials recorded with concentric electrodes: physiologic im-plications. Electroencephalogr Clin Neurophysiol 1997;105:333–339.

25. Dumitru D, King JC, Rogers WE. Motor unit action potentialcomponents and physiologic duration. Muscle Nerve 1999;22:733–741.

26. Dumitru D, King JC, Rogers WE, Stegeman DF. Positive sharpwave and fibrillation potential modeling. Muscle Nerve 1999;22:242–251.

27. Dumitru D, King JC, Stegeman DF. Endplate spike morphol-ogy: a clinical and simulation study. Arch Phys Med Rehabil1998;79:634–640.

28. Dumitru D, King JC, Stegeman DF. Normal needle electro-myographic insertional activity morphology: a clinical andstimulation study. Muscle Nerve 1998;21:910–920.

29. Elmqvist D. Neuromuscular transmission defects. In: DesmedtJE, editor. New developments in electromyography and clini-cal neurophysiology. Vol 1. Basel: Karger; 1973; p 229–240.

30. Elmqvist D, Quastel DMJ. A quantitative study of endplatepotentials in isolated human muscle. J Physiol 1965;178:505–529.

31. Engel WK. Focal myopathic changes produced by electromyo-graphic and hypodermic needles: “needle myopathy.” ArchNeurol 1967;16:509–511.

32. Franke C, Hatt H, Iaizzo PA, Lehmann-Horn F. Characteris-tics of Na+ channels and Cl− conductance in resealed musclefibre segments from patients with myotonic dystrophy. J Phys-iol 1990;425:391–405.

33. Gatens PF, Saeed MA. Electromyographic findings in the in-

trinsic muscles of normal feet. Arch Phys Med Rehabil 1982;63:317–318.

34. Green DS, George AL, Cannon SC. Human sodium channelgating defects caused by missense mutations in S6 segmentsassociated with myotonia: S804F and V1293I. J Physiol199;510:685–694.

35. Guyton AC. Textbook of medical physiology. 8th ed. Phila-delphia: Saunders; 1991. p 38–50.

36. Hayward LJ, Brown RH, Cannon SC. Inactivation defectscaused by myotonia-associated mutations in the sodium chan-nel III–IV linker. J Gen Physiol 1996;107:559–576.

37. Hayward LJ, Sandoval GM, Cannon SC. Defective slow inac-tivation of sodium channels contributes to familial periodicparalysis. Neurology 1999;52:1447–1453.

38. Hille B. Introduction to physiology of excitable cells. In: Pat-ton HD, Fuchs AF, Hille B, Scher AM, Steiner R, editors.Textbook of physiology: excitable cells and neurophysiology.21st ed. Philadelphia: Saunders; 1989. p 1–23.

39. Hille B. Ionic basis of resting potentials and action potentials.In: Kandel ER, editor. Handbook of physiology; section 1, Vol1. Bethesda, MD: American Physiological Society; 1977. p99–136.

40. Hodgkin AL, Huxley AF. Currents carried by sodium andpotassium ions through the membrane of the giant axon ofLoligo. J Physiol 1952;116:449–472.

41. Hodgkin AL, Huxley AF, Katz B. Measurement of current-voltage relations in the membrane of the giant axon of Lo-ligo. J Physiol 1952;116:424–448.

42. Hugues M, Schmid H, Romey G, Duval D, Frelin C, LazdunskiM. The Ca2+ dependent slow K+ conductance in cultured ratmuscle cells: characterization with apamin. EMBO J 1982;1:1039–1042.

43. Jarcho LW, Berman B, Dowben RM, Lilienthal JL. Site oforigin and velocity of conduction of fibrillary potentials indenervated skeletal muscle. Am J Physiol 1954;1788:129–134.

44. Jentsch TJ, Friedrich T, Schriever A, Yamada H. The CLCchloride channel family. Pflugers Arch 1999;437:783–795.

45. Jewett DL, Deupress DL. Far-field potentials recorded fromaction potentials and from a tripole in a hemicylindrical vol-ume. Electroencephalogr Clin Neurophysiol 1989;72:439–449.

46. Katz B. Nerve, muscle, synapse. New York: McGraw-Hill; 1966.193 p.

47. Kincaid JC, Brasher A, Markand ON. The influence of thereference electrode on CMAP configuration. Muscle Nerve1993;16:392–396.

48. Kobayashi T, Askanas V, Saito K, Engel WK, Ishikawa K. Ab-normalities of aneural and innervated cultured muscle fibersfrom patients with myotonic atrophy (dystrophy). Arch Neu-rology 1990;47:893–896.

49. Koester J. Resting membrane potential and action potential.In: Kandel ER, Schwartz JH, editors. Principles of neurosci-ence. 2nd ed. New York: Elsevier; 1985. p 49–57.

50. Kotsias BA, Venosa RA. Role of sodium and potassium per-meabilities in the depolarization of denervated rat musclefibres. J Physiol 1987;392:301–313.

51. Kugelberg E. “Insertional activity” in electromyography. JNeurol Neurosurg Psychiatry 1949;29:268–273.

52. Lehmann-Horn F, Iaizzo PA, Franke C, Hatt H, Spaans F. Adefect of sodium channels causes myotonia in a patient withSchwartz-Jampel syndrome. Muscle Nerve 1990;13:528–535.

53. Lehmann-Horn F, Jurkat-Rott K. Voltage-gated ion channelsand hereditary disease. Physiol Rev 1999;79:1317–1372.

54. Lerche H, Heine R, Pika U, George AL, Mitrovic N, BrowatzkiM, Weib T, Rivet-Bastide M, Franke C, Lomonaco M, RickerK, Lehmann-Horn F. Human sodium channel myotonia:slowed channel inactivation due to substitutions for glycinewithin the III–IV linker. J Physiol 1993;470:13–22.

55. Ludin HP. Microelectrode study of normal human skeletalmuscle. Eur Neurol 1969;2:340–347.

56. MacFarlane WV, Meares JD. Intracellular recording of action


and after-potentials of frog muscle between 0 and 45°C. JPhysiol 1958;142:97–109.

57. McCormick DA. Membrane potential and action potential.In: Zigmond MJ, Bloom FE, Landis SC, Roberts JL, Squire RL,editors. Fundamental neuroscience. San Diego: AcademicPress; 1999. p 129–154.

58. McGill KC, Lateva ZC. The contribution of the interosseousmuscles to the hypothenar compound muscle action poten-tial. Muscle Nerve 1999;22:6–15.

59. Merickel M, Gray R, Chauvin P, Appel S. Cultured musclefrom myotonic muscular dystrophy patients: altered mem-brane electrical properties. Proc Natl Acad Sci USA 1981;81:648–652.

60. Mitrovic N, Lerche H, Heine R, Fleischhauer R, Pika-HartlaubU, Hartlaub U, George AL, Lehmann-Horn F. Role of fastinactivation of conserved amino acids in the IV/S4-S5 loop ofthe human muscle Na+ channel. Neurosci Lett 1996;214:9–12.

61. Moxley RT. The myotonias: their diagnosis and treatment.Compr Ther 1996;22:8–21.

62. Moxley RT, Udd B, Rickert K. 54th ENMC international work-shop. PROMM (Proximal myotonic myopathies) and otherproximal myotonic syndromes, 10–12 October 1997, Na-arden, The Netherlands. Neuromuscul Disord 1998;8:508–518.

63. Nandedkar SD, Dumitru D, King JC. Concentric needle elec-trode duration measurements and uptake area. Muscle Nerve1997;20:1225–1228.

64. Nardin RA, Raynor EM, Rutkove SB. Fibrillation in lumbosa-cral paraspinal muscles of normal subjects. Muscle Nerve1998;21:1347–1349.

65. Nunez PL. Electric fields of the brain: the neurophysiology ofEEG. New York: Oxford University Press; 1981. p 80–90.

66. Plonsey R. Bioelectric phenomena. New York: McGraw-Hill;1969. 380 p.

67. Ptacek L. The familial periodic paralyses and nondystrophicmyotonias. Am J Med 1998;105:58–70.

68. Purves D, Sakman B. Membrane properties underlying spon-taneous activity of denervated muscle fibers. J Physiol 1974;239:125–153.

69. Redfern P, Thesleff S. Action potential generation in dener-

vated rat skeletal muscle: I. Quantitative aspects. Acta PhysiolScand 1971;81:557–564.

70. Rudel R, Lehmann-Horn F. Membrane changes in cells frommyotonia patients. Physiol Rev 1985;65:310–356.

71. Ruff RL. Alterations of Na+ channel gating in myotonia. JPhysiol 1997;499:571–575.

72. Schmid-Antomarchi H, Renaud J, Romey G, Hughes M,Schmid A, Lazdunski M. The all-or-none role of innervationin expression of apamin receptor and of apamin-sensitiveCa2+-activated K+ channel in mammalian skeletal muscle.Proc Natl Acad Sci USA 1985;82:2188–2191.

73. Stegeman DF, Dumitru D, King JC, Roeleveld K. Near- andfar-fields: source characteristics and the conducting mediumin neurophysiology. J Clin Neurophysiol 1997;14:429–442.

74. Stohr M. Benign fibrillation potentials in normal muscle andtheir correlation with endplate and denervation potentials. JNeurol Neurosurg Psychiatry 1977;40:765–768.

75. Thesleff S. Fibrillation in denervated mamallian muscle. In:Culp WJ, Ochoa J, editors. Abnormal nerves and muscle gen-erators. New York: Oxford University Press; 1982. p 678–694.

76. Thesleff S. Spontaneous electrical activity in denervated ratskeletal muscle. In: Gutmann E, Hnik P, editors. The effect ofuse and disuse on neuromuscular functions. Prague: Publish-ing House of Czechoslovak Academy of Sciences; 1963. p41–51.

77. Thesleff S, Ward MR. Studies on the mechanism of fibrillationpotentials in denervated muscle. J Physiol 1975;244:313–323.

78. Wiechers D, Guyton JD, Johnson EW. Electromyographicfindings in the extensor digitorum brevis in a normal popu-lation. Arch Phys Med Rehabil 1976;57:84–85.

79. Wiechers DO. Electromyographic insertional activity in nor-mal limb muscles. Arch Phys Med Rehabil 1979;60:359–363.

80. Wiechers DO. Mechanically provoked insertional activity be-fore and after nerve section in rats. Arch Phys Med Rehabil1977;58:402–405.

81. Wiechers DO, Stow R, Johnson EW. Electromyographic inser-tional activity mechanically provoked in the biceps brachiimuscle. Arch Phys Med Rehabil 1977;58:573–578.

82. Wiederholt WC. “Endplate noise” in electromyography. Neu-rology 1970;20:214–224.


physiologic basis of potentials recorded in electromyography

Documents