Action Potentials in Different Nerve MembranesAP = A membrane potential change caused by a flow of ions through ion channels in the membrane

Intracellular RecordingTwo Points, Ea and Eb

Conduction Velocity (cv) =Probagation time/distancebetween a and b

Node of Ranvier:Depolarize then Spike

Motoneuron, Squid Axon:Shocked away from a Latency is distance Traveled.

Conduction Velocity butNot Channel Conductance is Temperature Dependent

Hermann’s Cable Theory: Passive spread of APsSimilar to a Leaky Telegraph Cable

Re = extracellular membrane resistanceRi = cytoplasmic membrane resistanceRm = variable dependent upon channel gatingthat causes change in emfCm = membrane as parallel plate capacitor

“These two elements may be just different aspects of the samemembrane mechanism” Cole and Curtis 1938

Action Potentials: 1, Underlying ionic basis = Na and K channels2. All or none3. Propagated by passive spread of electrotonic currents4. Restriction of ion channel expression – Example Node of Ranvier and Saltatory Conduction

Nav1.6 and Kv1.2 (See Plate 1)5. Ion channels have no thresholds for activation. AP 15% TH6. Code is not in the width or height of the AP – Information code = The Frequency

Voltage-clamp Electrophysiology – Approach is PreparationDependent – Best Biophysical Technique to Study Ion Channel Activity

E’ = recording electrodeI” = current injecting electrodeFBA = feedback amplifier (Px changes can be rapid and FBAwith high freq. response has to readjust the current injection constantly )

Principle: Vc is set by investigatorSimultaneously Acts as a Voltage Sensor (E’) and CurrentInjector (I’)

Best Utility for These 3:Two MicroelectrodeSuction PipettePatch Clamp

Im = Ii + Ic = Ii +Cm dE dt

First Recordings of Current by Hodgkin, Huxley, and KatzIonic Theory of Membrane ExcitationClassical Biophysics Period (1935-1952)

The Independence Relation: First recognized that currentcould be separated into components carried by differentions.

First to use the approach of Ion Substitution

1. Observed Biphasic Current when Hyperpolarized.

2. Choline Chloride forNao

3. Algebraic DifferenceTo Derive the INa

HH Model to Determine the H Infinity Curve for Na Channel Inactivation

Activation: rapid process that opens Na channels during a depolarization

Inactivation: process that closes Na channels during a depolarization; mustrepolarize membrane to release channels from inactivated state

Recovery from Inactivation Curves

Why are there MANY different types of of Na and K channels even within the same species but across different tissues/organs?

Na ChannelsAlpha, Beta1, Beta 2

Ca ChannelsAlpha1, alpha2, beta, gamma, delta

K Channels4 Alpha Beta

All V-gated Ion Channels –1. Glycosylation, esp. eukaryotic2. Principle and Auxillary subunits

a. Principle:toxin-binding sitesS4 voltage sensorporegateselectivity filterb. Auxillarymembrane trafficking to the PMalteration of inactivation

3. Protein-protein interactions

External Ion Channel Pore Blockers to Isolate gNa vs. gK

Armstrong’s Experiments: Internal TEA BlockIncoming K flux knocked out TEAi, therefore must beA Pore! Flux rate determined as 600 ions/millisecond.

Myelination allowed increase conduction velocity of APs through Saltatory Conduction across the Nodes of Ranvier

Localization of Ion Channels: Nav1.6 and Kv1.2 (See Plate 1)

Tau = Rm x Cm

How did invertebrateorganisms increaseconduction velocity?

What is the evolutionaryadvantage of myelin?

Do Current Biophysical Properties Deliniate a Different Gene?

Human gene names = all capital lettersNon-human mammalian = lower caseGene names are always in italics