Roles of two ryanodine receptor isoforms coexisting in skeletal muscle

Ryanodine receptor (RyR) is a Ca(2)(+) release channel in the sarcoplasmic reticulum and plays an important role in excitation-contraction coupling in skeletal muscle. The Ca(2)(+) release through the RyR channel can be gated by two distinct modes: depolarization-induced Ca(2)(+) release (DICR) and Ca(2)(+)-induced Ca(2)(+) release (CICR). Two different RyR isoforms, RyR1 (or alpha-RyR) and RyR3 (or beta-RyR), have been found to be expressed in skeletal muscle. Most adult mammalian muscles express primarily RyR1, whereas almost equal amounts of the two RyR isoforms exist in many nonmammalian vertebrate muscles. RyR1 is believed to be responsible for both DICR and CICR, whereas RyR3 may function as the CICR channel. Recent findings demonstrate that alpha-RyR is selectively and markedly suppressed in CICR activity in frog skeletal muscle. This selective suppression of RyR1, although to a lesser extent, also was found to occur in mammalian skeletal muscle. This short review describes the biological meanings of this selective suppression and discusses physiological roles and significance of the two RyR isoforms in vertebrate skeletal muscle.