From excitation to intracellular Ca movements in skeletal muscle: Basic aspects and related clinical disorders.

In skeletal muscle fiber, excitation-contraction coupling corresponds to the sequence of events occurring from action potential firing to initiation of contraction by an increase in cytosolic Ca. These events are elicited in response to excitation of the motor neuron which induces trains of action potentials in the muscle cell that spread along the sarcolemma and in depth along the T-tubule membrane. Depolarization of the T-tubule membrane induces a conformational change in a protein complex, called the dihydropyridine receptor, which opens a calcium channel anchored in the membrane of the sarcoplasmic reticulum, called the ryanodine receptor, in charge of release of Ca ions that activate contractile proteins. Ryanodine receptors shut upon return of the T-tubule membrane potential to its resting value and muscle cell relaxation results from the removal of cytosolic Ca that is pumped back into the SR lumen through the sarcoplasmic reticulum Ca ATPase. Mutations in genes encoding either plasma membrane ion channels, the main subunit of the dihydropyridine receptor, ryanodine receptor, sarcoplasmic reticulum Ca ATPase or proteins interfering with trans-sarcolemmal Ca influx or sarcoplasmic reticulum Ca efflux lead to clinical disorders that manifest as myotonia, muscle weakness, paralysis or muscle wasting.