Muscle excitation and excitation-contraction coupling

Lecture 3

What is a motor endplate/motor terminal?

Motor axons that split into branches

each branch attaches to a single muscle fibre

attachment near the central region of the fibre

What makes up a motor unit?

presynaptic neuron and the collection of muscle fibres it innervates (all the same type of muscle fibre)

What does the attenuation of action potentials imply?

pre-synaptically evoked muscle action potential must initiate in the area immediately around the endplate.

structure of transverse ‘T’ tubular system

invaginations of the surface membrane

lumen remains continuous with extracellular space and penetrates into interior of muscle fibre

resulting network surrounds each individual myofibril

Where do T networks occur?

junctions between A & I bands in skeletal muscle

Z line in cardiac muscle

What is the triad arrangement?

sarcoplasmic reticulum forms longitudinal system of tubules & sacs which contain terminal cisternae

2 terminal cisternae sandwiching 1 T tubule = triad

How does Cl^- keep the membrane potential of the T-system well-polarised?

T-system more permeable to Cl^- than K⁺ at rest

equilibrium potential for Cl^- similar to resting membrane potential

myotonia congenita

Cl^- channels are defective

train of action potentials results in T-system depolarisation

causes involuntary tetanic muscle contractions after stimulus has ceased

dihydropyridine receptors

voltage sensors & Ca²⁺ channels in the membrane of the T-tubules

mechanically linked to ryanodine receptors in sarcoplasmic reticulum

ryanodine receptors

calcium release channels in the sarcoplasmic reticulum

mechanically linked the dihydropyridine receptors.

Calcium induced calcium release

depolarisation of T-tubule membrane

conformational change in dihydropyridine receptors

directly produces a conformational change in ryanodine receptors

calcium channels open

Ca²⁺ flows down electrochemical gradient out of sarcoplasmic reticulum

contraction initiated when Ca²⁺ binds to TnC

How is Ca²⁺ stored in the muscle fibre?

concentrated in sarcoplasmic reticulum by ATP-consuming Ca²⁺ pumps (SERCA pumps) where much is bound to calcium-binding proteins like calsequestrin.

reduces the gradient against which the pump has to work.

malignant hyperthermia

life-threatening reaction to general anaesthetic

genetic defect in ryanodine receptors —→ over-release of calcium —→ constant maximal SERCA pump activity —→ contractions —→ lactic acid buildup

hyperthermia, tachycardia, muscle breakdown

Treatment: dantrolene - ryanodine receptor blocker

Hyperkalaemic periodic paralysis & paramyotonia congenita

mutations in Na⁺ channels

defects in inactivation

inability to relax properly after contraction

myotonia congenita

mutations in ClC1 chloride channel causes defective repolarisation

contractions fail to terminate normally