Regulation of depolarization-induced calcium release from skeletal muscle triads by cyclic AMP-dependent protein kinase

cAMP activated Ca2+ release from the sarcoplasmic reticulum (SR) triggered by transverse tubular membrane depolarization monitored in a triadic vesicle prepared from rabbit skeletal muscle. A kinetic analysis showed that the activation was in the amounts of released Ca2+ and not in the release rates. This activation was found to be depolarization-dependent, that is, the activation effect of cAMP decreased with an increase in the magnitude of depolarization. Because the activation was abolished by a protein kinase inhibitor, protein phosphorylation by the endogenous cAMP-dependent protein kinase (PKA) was thought to be in effect. On the contrary, caffeine-induced Ca2+ release was not activated by cAMP; however, the exogenous PKA catalytic subunit activated Ca2+ release, and this effect was probably through the phosphorylation of the SR Ca2+ release channel as described elsewhere. These results suggest that the protein, except for the SR Ca2+ release channel, is phosphorylated by endogenous PKA and plays a modulatory role in depolarization-induced Ca2+ release, that is, excitation-contraction coupling of the skeletal muscle.