Inositol Trisphosphate Enhances Calcium Release in Skinned Cardiac and Skeletal Muscle

Experiments from other laboratories suggest that inositol trisphosphate (InsP3) may be involved in the excitation-contraction coupling (ECC) process of cardiac and skeletal muscle. Our results support this hypothesis. Studying fiber bundles (less than 200-microns diameter) from guinea pig papillary muscles skinned with saponin and mechanically skinned single fibers from frog semitendinosus muscle, we find that calcium-induced force oscillations (observed in solutions containing low ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid and pCa 7.0) are enhanced in magnitude and frequency by InsP3 at concentrations as low as 1 microM. InsP3 at 10 microM can often induce such oscillations in mechanically skinned frog skeletal muscle. In skinned cardiac fibers, InsP3 increases the magnitude of caffeine contractures at submaximal caffeine concentrations to a greater extent than at near-maximal caffeine concentrations. InsP3 (30 microM) has no effect on either the calcium sensitivity or maximal force generated by the contractile apparatus of skinned cardiac muscle. We conclude that InsP3 has no direct effect on the contractile machinery but that it can modulate ECC by enhancing the calcium-induced release of calcium from the sarcoplasmic reticulum, possibly from the same pool and through the same mechanism as caffeine.