Inositol 1,4,5-trisphosphate-induced Ca2+ release is regulated by cytosolic Ca2+ in intact skeletal muscle.
Microinjection of inositol 1,4,5-trisphosphate (InsP3) into intact skeletal 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 InsP3-induced release of cytosolic Ca2+. Neither ruthenium red, a blocker of ryanodine receptor Ca2+-release channels, nor cytosolic Mg2+, a known inhibitor of the Ca2+-induced Ca2+-release process, modified the InsP3-induced release of cytosolic Ca2+. However, heparin, a blocker of InsP3 receptors, inhibited InsP3-induced release of cytosolic Ca2+. Also, pretreatment with dantrolene or azumulene, two inhibitors of cytosolic Ca2+ release, reduced [Ca2+]i, and prevented InsP3 from inducing release of cytosolic Ca2+. Incubation in caffeine or lengthening of the muscle increased [Ca2+]i and enhanced the ability of InsP3 to induce release of cytosolic Ca2+. These results indicate that InsP3, at physiological concentrations, induces Ca2+ release in intact muscle fibers, and suggest that the InsP3-induced Ca2+ release is regulated by [Ca2+]i. A Ca2+-dependent effect of InsP3 on cytosolic Ca2+ release could be of importance under physiological or pathophysiological conditions associated with alterations in cytosolic Ca2+ homeostasis.
López
J R
JR
Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Terzic
A
A
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D011896:Rana temporaria; D012430:Ruthenium Red / Q000494:pharmacology
D012430:Ruthenium Red; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D009568:Nitrendipine; D003620:Dantrolene; D008274:Magnesium; D002118:Calcium