Calcium Dependence of Muscle Contraction

Acetylcholine Release at the Neuromuscular Junction

• Initiating event: Motor neuron arrives at the neuromuscular junction (NMJ) and releases the neurotransmitter acetylcholine (ACh) into the synaptic cleft.

• Target: ACh diffuses across the cleft and binds to nicotinic acetylcholine receptors (nAChR) located on the motor end‐plate of the skeletal muscle fiber.

• Receptor type: nAChRs are ligand-gated sodium (Na⁺) channels—binding of ACh opens these channels.

Sodium Influx and Depolarization of the Sarcolemma

• Ion movement: Once nAChRs open, Na⁺ rushes into the muscle cell following its electrochemical gradient.

  • Key property: Na⁺ carries a positive charge.

• Electrical consequence: The influx of positive Na⁺ ions causes the membrane potential to become less negative (depolarization).

  • If we denote resting potential as $V_{rest} \approx -90\, \text{mV}$, then a sufficient Na⁺ influx can raise the potential toward the threshold for an action potential.

• Local end-plate potential (EPP): This initial depolarization is termed the end-plate potential, which—if large enough—triggers a muscle action potential.

Propagation Through T-Tubules

• Sarcolemma vs. T-tubules: The sarcolemma (muscle fiber plasma membrane) invaginates deep into the fiber forming transverse (T) tubules.

• Purpose: These T-tubules rapidly conduct the depolarization wave from the surface throughout the interior of the muscle fiber, ensuring simultaneous activation.

Activation of the Sarcoplasmic Reticulum (SR)

• Organelle equivalence: The sarcoplasmic reticulum (SR) is functionally analogous to the endoplasmic reticulum but specialized for Ca²⁺ storage in muscle cells.

• Voltage sensing: Depolarization in the T-tubule membrane activates voltage-sensitive dihydropyridine receptors (DHPR) that are mechanically or chemically linked to ryanodine receptors (RyR) on the SR.

• Calcium release: This coupling opens voltage-gated Ca²⁺ channels in the SR, allowing Ca²⁺ to flood into the sarcoplasm.

  • Typical SR Ca²⁺ concentration: $[Ca^{2+}]<em>{SR} \gg [Ca^{2+}]</em>{cytosol}$ creating a steep gradient.

Calcium’s Role in Triggering Contraction (Preview)

• Immediate consequence: The rise in cytosolic Ca²⁺ concentration initiates the cross-bridge cycle by binding to troponin C on the thin filament.

• Result: This removes tropomyosin’s blockade of actin’s myosin-binding sites, permitting actin-myosin interaction and ultimately muscle contraction.