Postulated role of inter-domain interaction within the ryanodine receptor in Ca2+ channel regulation

Key steps of excitation-contraction (E-C) coupling ave (1) binding of the activator portion of the dihydropyridine (DHP) receptor (in skeletal muscle) or binding of the Ca2+ entered through the DHP receptor (in cardiac muscle) to the ryanodine receptor (RyR), (2) a global protein conformational change of the RyR, and (3) opening of the RyR Ca2+ channel, leading to muscle contraction. The conformational change (step 2) plays a major role in the Ca2+ channel regulation, and a number of "regulatory domains" must be involved in this process. We postulate that the interaction among these regulatory domains is the central mechanism for the conformation-mediated control of the Ca2+ channel. In this review, we summarize the recent data supporting this concept. (Trends Cardiovasc Med 2000;10:310-316). (C) 2000, Elsevier Science Inc.