Fatty acyl-CoA esters induce calcium release from terminal cisternae of skeletal muscle.
The effect of palmitoyl-CoA (PCoA) on Ca2+ fluxes in unfractionated SR, longitudinal tubules (LSR) and terminal cisternae (TC) subfractions, obtained from rabbit fast-twitch skeletal muscles, was investigated. After MgATP-dependent Ca2+ preloading, PCoA released Ca2+ from unfractionated SR and TC, but not from LSR. Both the extent and the rate of PCoA-induced Ca2+ release from TC were increased in a dose-dependent manner, the half-maximal effect being attained at [PCoA] of approximately 6 microM. Ruthenium red, a Ca2+ release channel blocker, completely inhibited PCoA-induced Ca2+ release, whereas caffeine, a Ca2+ release channel agonist, depleted TC of Ca2+ and prevented the PCoA action. Scatchard plot analysis of [3H]-ryanodine binding showed that PCoA increased the affinity without affecting Bmax. The action of PCoA was mimicked by a nonhydrolysable analog. The present results indicate that PCoA interacts and opens the Ca2+ release channel (ryanodine receptor) of TC and that the mechanism of action involves binding rather than hydrolysis.
Fulceri
R
R
Istituto di Patologia Generale, University of Siena, Italy.
Nori
A
A
Gamberucci
A
A
Volpe
P
P
Giunti
R
R
Benedetti
A
A
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D011817:Rabbits; D013997:Time Factors
D000214:Acyl Coenzyme A; D002110:Caffeine; D002118:Calcium