MOLECULAR GENETICS OF EXCIATION-CONTRACTION COUPLING

The process that, following nerve stimulation, results in calcium release and activation of muscle contraction is called excitation-contraction coupling. In striated muscles, protein complexes of specific composition are assembled on the sarcolemma and the sarcoplasmic reticulum where they form a “molecular machine” dedicated to this function. Two proteins, the ryanodine receptor type 1 (RyR1) and the dihydropyridine receptor, are known as essential players in this mechanism. However there is evidence that also other proteins, among which RyR3 channels, participate of this mechanism and play a role in optimising muscle contraction or in the organisation of the components of the molecular machine that underlies the excitation-contraction coupling mechanism. It is well known that muscle diseases can be caused by mutations of proteins directly involved in the excitation-contraction coupling mechanisms. It can be expected that the identification and characterisation of new proteins participating of excitation-contraction coupling may lead to a better understanding, diagnosis and eventually new forms of therapeutic intervention for neuromuscular and other genetic disease in a near future.