Fatty acyl-CoA esters induce calcium release from terminal cisternae of skeletal muscle

The effect of palmitoyl-CoA (PCoA) on Ca 2+ fluxes in unfractionated SR, longitudinal tubules (LSR) and terminal cisternae (TC) subfractions, obtained from rabbit fast-twitch skeletal muscles, was investigated. After MgATP-dependent Ca 2+ preloading, PCoA released Ca 2+ from unfractionated SR and TC, but not from LSR. Both the extent and the rate of PCoA-induced Ca 2+ release from TC were increased in a dose-dependent manner, the half-maximal effect being attained at [PCoA] of approximately 6 μM. Ruthenium red, a Ca 2+ release channel blocker, completely inhibited PCoA-induced Ca 2+ release, whereas caffeine, a Ca 2+ release channel agonist, depleted TC of Ca 2+ and prevented the PCoA action. Scatchard plot analysis of [ 3H]-ryanodine binding showed that PCoA increased the affinity without affecting B max. The action of PCoA was mimicked by a nonhydrolysable analog. The present results indicate that PCoA interacts and opens the Ca 2+ release channel (ryanodine receptor) of TC and that the mechanism of action involves binding rather than hydrolysis.