What is most directly responsible for the coupling of excitation to contraction of skeletal muscle fibers?

Answer 1

Skeletal muscleIn skeletal muscle the method of excitation contraction coupling relies on the ryanodine receptor being activated by a domain spanning the space between the T tubules and the sarcoplasmic reticulum to produce the calcium transient responsible for allowing contraction.

1. The alpha motor neuron produces an action potential that propagates down its axon to the neuromuscular junction.
2. The action potential is sensed by a voltage-dependent calcium channel which causes an influx of Ca2+ ions which causes exocytosis of synaptic vesicles containing acetylcholine.
3. Acetylcholine diffuses across the synapse and binds to nicotinic acetylcholine receptors on the myocyte, which causes an influx of Na+ and an efflux of K+ and generation of an end-plate potential.
4. The end-plate potential propagates throughout the myocyte's sarcolemma and into the T-tubule system.
5. The T-tubule contains dihydropyridine receptors which are voltage-dependent calcium channels and are activated by the action potential.
6. The dihydropyridine receptors transmit the voltage-mediated signal through a mechanical linkage to the ryanodine receptors in the sarcoplasmic reticulum.
7. Ryanodine receptors undergo a conformational change that opens their channel.
8. Opening of the Ryanodine receptors causes and flow of Ca2+ from the sarcoplasmic reticulum into the cytoplasm. In this release, Ca2+ unbinds from the calcium-binding protein called calsequestrin.
9. Ca2+ released from the sarcoplasmic reticulum binds to Troponin C on actin filaments, which subsequently leads to the troponin complex being physically moved aside to uncover cross-bridge binding sites on the actin filament.
10. By hydrolyzing ATP, myosin forms a cross bridges with the actin filaments, and pulls the actin toward the center of the sarcomere resulting in contraction of the sarcomere.
11. Activation of the cross-bridge cycling may induce a shortening of the sarcomeres and the muscle as a whole, but not if the tension is insufficient to overcome the load imparted on the muscle.
12. Simultaneously, the sarco/endoplasmic reticulum Ca2+-ATPase actively pumps Ca2+ back into the sarcoplasmic reticulum where Ca2+ rebinds to calsequestrin.
13. With Ca2+ no longer bound to troponin C, the troponin complex slips back to its blocking position over the binding sites on actin.
14. Since cross-bridge cycling is ceasing then the load on the muscle causes the inactive sarcomeres to lengthen.

Cardiac muscle

In cardiac muscle, the method is dependent on a phenomenon called calcium-induced calcium release, which involves the conduction of calcium ions into the cell triggering further release of ions into the cytoplasm (about 75% of calcium present in the cytoplasm during contraction is release from the sarcoplasmic reticulum).

1. An action potential is induced by pacemaker cells in the Sinoatrial node or Atrioventricular node and conducted from non-contractile cardiac myocytes to contractile cells through gap junctions.
2. The action potential triggers L-type calcium channels during the plateau phase of the cardiac action potential, causing a net flux of calcium ions into the cardiac myocyte.
3. The increase in intracellular calcium ions is detected by ryanodine receptors in the membrane of the sarcoplasmic reticulum which transport calcium out into the cytosol in a positive feedback physiological response.
4. The cytoplasmic calcium binds to Troponin C, moving the troponin complex off the actin binding site allowing the myosin head to bind to the actin filament.
5. Using ATP hydrolysis the myosin head pulls the actin filament to the centre of the sarcomere.
6. Intracellular calcium is taken up by the sarco/endoplasmic reticulum ATPase pump into the sarcoplasm, or ejected from the cell by the sodium-calcium exchanger or the plasma membrane calcium ATPase.
7. Intracellular calcium concentration drops and troponin complex returns over the active site of the actin filament, ending contraction.

Answer 2

Calcium ion