Excitation-Contraction Coupling

Troponin C: Binds to calcium to activate actin:myosin interaction

Troponin T: Binds to tropomyosin

Troponin I: Blocks or inhibits actin:myosin interaction

Why CCBs such as verapamil does not have effect on skeletal muscles?

Skeletal muscle is resistant to the effect of calcium channel blockers because it does NOT require an influx of extracellular calcium for excitation-contraction coupling, whereas cardiac and smooth muscle depend on extracellular calcium entering the cell via voltage-gated L-type calcium channels for excitation-contraction coupling.

These voltage-gated calcium channels are the target of CCBs such as verapamil.

Muscle contraction

Major steps:

• action potential reaches the neuromuscular junction, causing a calcium ion influx through voltage-gated calcium channels
• the calcium influx causes the release of acetylcholine into the extracellular space
• the acetylcholine activates nicotinic acetylcholine receptors causing an influx of sodium, triggering an action potential
• the action potential spreads through the T-tubules
• the depolarization activates L-type voltage-dependent calcium channels (dihydropyridine receptors) in the T-tubule membrane, which are close to calcium-release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum
• this causes the sarcoplasmic reticulum to release calcium
• calcium binds to troponin C (found on actin-containing thin filaments) causing a conformational change, allowing tropomyosin to move, unblocking the binding sites