THE ROLE OF PHOSPHOINOSITIDE METABOLISM IN CA2-MUSCLE CELLS( SIGNALING OF SKELETAL)

1. The mobilization of Ca2+ from intracellular stores by D-myo-inosito l 1,4,5-triphosphate[Ins(1,4,5)P-3] is now widely accepted as the prim ary link between plasma membrane receptors that stimulate phospholipas e C and the subsequent increase in intracellular free Ca2+ that occurs when such receptors are activated (Berridge, 1993). Since the observa tions of Volpe et al. (1985) which showed that Ins(1,4,5)P-3 could ind uce Ca2+ release from isolated terminal cisternae membranes and elicit contracture of chemically skinned muscle fibres, research has focused on the role of Ins(1,4,5)P-3 in the generation of SR Ca2+ transients and in the mechanism of excitation-contraction coupling (EC-coupling). 2. The mechanism of signal transduction at the triadic junction durin g EC-coupling is unknown. Asymmetric charge movement and mechanical co upling between highly specialized triadic proteins has been proposed a s the primary mechanism for voltage-activated generation of SR Ca2+ si gnals and subsequent contraction. Ins(1,4,5)P-3 has also been proposed as the major signal transduction molecule for the generation of the p rimary Ca2+ transient produced during EC-coupling.