neurophysiology and skeletal muscle physiology

Ageing and Endings A

Neurophysiology and Skeletal Muscle Physiology

Matt Schiller of 5

Membrane Transport

Description

Energy required

Examples

Simple diffusion

Lipid-soluble substances can pass directly through phospholipid bilayer

Obeys Fick’s Law of diffusion rate or flux

Passive Water

Urea

Facilitated diffusion

Carrier (no continuous pore) or channel (continuous pore) proteins in membrane

Molecules move down electrochemical gradient

Compared to simple diffusion, has higher flux rates, saturability, specificity and selectivity

Passive Potassium channels

Primary active transport

Movement of molecules against electrochemical gradient

Coupled to utilisation of chemical energy

ATP Sodium-potassium-ATPase

Secondary active transport

Use of an existing ion gradient (generally sodium) to move another molecule against its electrochemical gradient

Co-transport/symport or counter-transport/antiport

Ion gradient

Sodium-glucose symporter

Sodium-calcium exchanger

Four main types of membrane transport Types of ion channel gating:

Extracellular ligand. Intracellular ligand. Voltage. Stretch. Background or leak channels.

Action Potential Propagation

Mechanism of regenerative propagation: Triggering event opens sodium channels, causing depolarisation. Depolarisation opens adjacent voltage-gated sodium channels.

Cycle of depolarisation and channel opening continues. Transient deactivation of sodium channels allows unidirectional propagation.

No loss of signal, unlike passive spread of depolarisation (‘all or nothing’). Conduction velocity is determined by how easily and quickly local polarisation can

cause the adjacent section of axon to reach threshold and active voltage-determined sodium channels, and proportional to:

Myelination (markedly increases membrane resistance, but does not affect internal resistance).

Axon diameter. Temperature.



Matt Schiller of 5

Action potential propagation Action Potential Phases

-70

0

65 (ENa+)

-90 (EK+)

Threshold

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Closed Open

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Closed

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Closed Open Closed Closed

Able to open Unable

to open

Able to open

POTASSIUM CHANNELS

SODIUM CHANNELS

ME

MB

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(Mv)



Matt Schiller of 5

Stages of Synaptic Transmission

Depolarisation reaches presynaptic terminal. Opening of voltage-gated calcium channels and increased calcium concentration in

presynaptic terminal.

Calcium triggers fusion of synaptic vesicles to presynaptic membrane (via v-SNAREs on vesicle and t-SNAREs on membrane).

Neurotransmitter release and diffusion across synaptic cleft. Binding of neurotransmitter with ligand-gated postsynaptic channels. Neuromuscular Junctions and Motor Units Neuromuscular junction (NMJ) – synapse between a motor axon and a muscle fibre:

One per muscle fibre, but multiple per axon.

Involves spatially-opposed specialisation of both the axon and the muscle fibre. Neurotransmitter is acetylcholine (ACh)

Neuromuscular junction

Central nervous system Autonomic nervous system

Receptor type Excitatory ionotropic

Excitatory or inhibitory ionotropic and metabotropic

Excitatory or inhibitory metabotropic

Active zones ~1,000 ~2 ~20

Potential caused by single axon

40-50 mV 0.2-0.5 mV Profound

Comparison of NMJ to other synapse types Typical end plate potential (EPP) causes vesicles to be released from ~100 (out of

~1,000) active zones, causing a potential of 40-50 mV.

EPP terminated by: Degradation of ACh by acetylcholinesterase.

Diffusion of ACh out of cleft. Axoplasmic Transport

Anterograde Retrograde

Mechanism Microtubule system of tracks, using kinesin/dynein motors that are energised by ATP

Substances transported

Synthesised proteins (packed by budding off in membrane-enclosed vesicles from Golgi apparatus

Material absorbed at terminals (e.g. trophic factors

Speed of transport

Fast - ~400 mm/day Slow (cytoskeletal and soluble proteins)

– ~2 mm/day

~250 mm day



Matt Schiller of 5

Skeletal Muscle Structure and Proteins

Skeletal muscle fibre – single elongated, multinucleated (~1,000 nuclei per centimetre), contractile cell.

Fibril/Myofibril – sub-division of a skeletal muscle fibre composed of 100-400 sarcomeres.

Sarcomere – repeating unit of skeletal muscle, being the smallest unit of contraction (defined as one Z line to the next).

Striated appearance of skeletal muscle fibres due to filamentous proteins: Myosin (thick and dark).

Actin (thin and light). Z line – anchoring point of actin filaments. M line – consists of proteins that act to stabilise myosin filaments.

Sarcomere structure

Group Protein Band/Line Role

Contractile Myosin A band Muscle contraction

Actin I band

Regulatory Troponin I band Prevention of constant contraction (rigor)

Tropomyosin I band

Structural M proteins M line Securing of myosin in centre of sarcomere

C proteins A band Stabilisation of A band

Alpha-actinin Z line Stabilisation of Z line

Titin Z line to M line (A band to I band)

Stabilisation of sarcomere and prevention of overextension

Nebulin Stabilisation of actin

Major skeletal muscle proteins Sarcolemma – cell membrane of skeletal muscle fibre.

Connective tissue sheaths: Endomysium – surrounding individual fibres. Perimysoium – surrounding muscle fascicles/bundles. Epimysium – surrounding entire muscle.

Structural protein framework allows transmission of force of contraction laterally to sarcolemma, basal lamina and connective tissue sheaths, from which transmission can occurs along sheaths to tendons.



Matt Schiller of 5

Skeletal Muscle Operation

Sliding filament theory: Muscle operates by the relative sliding of actin and myosin filaments. Sliding is caused by cross-bridges that project from myosin filaments interacting

with specific sites on actin filaments.

Cross-bridges have a limited range of movement (~10 nm). Cross-bridges act cyclically, splitting a molecule of ATP per cycle.

Maximum force is produced when the maximum number of sites of interaction are aligned (of which there are a finite number).

Regulation of contraction by tropomyosin and troponin: Troponin covers binding sites on actin filaments in resting state. Troponin has a calcium binding site for calcium released by nervous stimulation.

When calcium binds to troponin, a conformation change occurs that exposes binding sites on actin and allows skeletal muscle contraction.

Stages of muscle contraction and relaxation: Action potential in surface membrane. Action potential conducted down transverse tubules (T tubules) to sarcoplasmic

reticulum.

Excitation-contraction coupling – opening of channels in sarcoplasmic reticulum. Release of calcium from sarcoplasmic reticulum. Operation of cross-bridge cycle between contractile proteins (contraction). Calcium pump in sarcoplasmic reticulum causes re-compartmentalisation of

calcium. Cross-bridge detachment occurs (relaxation).

Types of contraction:

Isotonic contraction – where constant tension produces a change in muscle length.

Isometric contraction – where tension change is recorded while muscle length remains constant.

Twitch and fused tetanus:

Twitch – response of skeletal muscle to a single action potential. Fused tetanus – response of skeletal muscle to a high frequency of action

potentials (about four times that of a twitch).

Motor unit – a single motor neuron and the muscle fibres that it innervates (vary in size from several to over 1000 muscle fibres).

Size principle – smaller motor units are recruited before larger ones, permitting the application of fine forces in small increments.

Muscle force can be increased by increasing: Frequency of motor nerve firing. Motor unit recruitment.

Speed of contraction and relaxation

Force Size Fatigue resistance

Fast fibres Fast High Large Low

Slow fibres Slow Low Small High

Comparison of fast and slow skeletal muscle fibres

neurophysiology and skeletal muscle physiology

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