INOSITOL 1,4,5-TRISPHOSPHATE INDUCED CA2-MUSCLE( RELEASE IS REGULATEDBY CYTOSOLIC CA2+ IN INTACT SKELETAL)

Microinjection of inositol 1,4,5-trisphosphate (InsP(3)) into intact s keletal muscle fibers isolated from frogs (Rana temporaria) increased resting cytosolic Ca2+ concentration ([Ca2+](i)) as measured by double -barreled Ca2+-selective microelectrodes. In contrast, microinjection of inositol 1-phosphate, inositol 1,4-biphosphate, and inositol 1,4,5, 6-tetrakisphosphate did not induce changes in [Ca2+](i). Incubation in low-Ca2+ solution, or in the presence of L-type Ca2+ channel blockers did not affect InsP(3)-induced release of cytosolic Ca2+. Neither rut henium red, a blocker of ryanodine receptor Ca2+-release channels, nor cytosolic Mg2+, a known inhibitor of the Ca2+-induced Ca2+-release pr ocess. modified the InsP(3)-induced release of cytosolic Ca2+ However, heparin, a blocker of InsP(3) receptors, inhibited InsP(3)-induced re lease of cytosolic Ca2+ Also, pretreatment with dantrolene or azumulen e, two inhibitors of cytosolic Ca2+ release, reduced [Ca2+](i), and pr evented InsP(3) from inducing release of cytosolic Ca2+. Incubation in caffeine or lengthening of the muscle increased [Ca2+](i) and enhance d the ability of InsP(3) to induce release of cytosolic Ca2+. These re sults indicate that InsP(3), at physiological concentrations, induces Ca2+ release in intact muscle fibers, and suggest that the InsP(3)-ind uced Ca2+ release is regulated by [Ca2+](i). A Ca2+-dependent effect o f InsP(3) on cytosolic Ca2+ release could be of importance under physi ological or pathophysiological conditions associated with alterations in cytosolic Ca2+ homeostasis.