Excitation-contraction coupling in skeletal muscle: questions remaining after 50 years of research

The excitation-contraction coupling mechanism was defined as the entire sequence of reactions linking excitation of plasma membrane to activation of contraction in skeletal muscle. By using different techniques, their regulation and interactions have been studied during the last 50 years, defining until now the importance and origin of the calcium ion as a contractile activator and the main proteins involved in the whole mechanism. Furthermore, the study of the ultrastructural basis and pharmacological regulation of the excitation-contraction coupling phenomenon has begun. The excitation-contraction coupling is thought to be altered in situations as ageing, muscle fatigue and some muscle diseases. However, many questions remain to be answered. For example, (1) How excitation-contraction coupling develops and ages? (2) What role does it play in muscle fatigue and other diseases? (3) What is the nature of the interaction between the proteins believed to be involved? The present review describes excitation-contraction coupling in skeletal muscle and techniques used to better understand it as an introduction for discussing unanswered questions regarding excitation-contraction coupling.