Inositol 1,4,5-trisphosphate: a possible chemical link in excitation-contraction coupling in muscle

Abstract The role of inositol 1,4,5-trisphosphate (InsP3) in excitation-contraction coupling in skeletal muscle was investigated by several methods. The following results were obtained. InsP3 is released by electrical stimulation of muscles. Exogenous InsP3 releases calcium from skinned muscle fibers at relatively high doses under normal conditions but does so at very low concentrations when blockers of the InsP3 5-phosphatase are present. Blockers of InsP3 release are effective blockers of calcium transients elicited by electrical stimulation of muscle fibers. It is proposed that InsP3 acts as a chemical second messenger between transverse (T)-tubular membrane depolarization and calcium release from the sarcoplasmic reticulum in skeletal muscle.