Inositol 1,4,5-trisphosphate induces calcium release from sarcoplasmic reticulum of skeletal muscle

Abstract

The sarcoplasmic reticulum of skeletal muscle is a specialized form of endoplasmic reticulum1 that controls myoplasmic calcium concentration and, therefore, the contraction–relaxation cycle2. Ultrastructural studies3 have shown that the sarcoplasmic reticulum is a continuous but heterogeneous membranous network composed of longitudinal tubules that surround myofibrils and terminal cisternae. These cisternae are junctionally associated, via bridging structures called ‘feet’4, with sarcolemmal invaginations (the transverse tubules) to form the triadic junction4. Following transverse tubule depolarization, a signal, transmitted along the triadic junction, triggers Ca2+ release from terminal cisternae5,6, but the mechanism of this coupling is still unknown7. Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) has recently been shown to mobilize Ca2+ from intracellular stores, referable to endoplasmic reticulum, in a variety of cell types (see ref. 8 for review), including smooth muscle cells of the porcine coronary artery9 and canine .cardiac muscle cells10. Here we show that Ins(1,4,5)P3 (1) releases Ca2+ from isolated, purified sarcoplasmic reticulum fractions of rabbit fast-twitch skeletal muscle, the effect being more pronounced on a fraction of terminal cisternae that contains morphologically intact feet structures11 ; and (2) elicits isometric force development in chemically skinned muscle fibres.