Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycolytic skeletal muscle.
Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near-maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained.
Garetto
L P
LP
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616.
Carlsen
R C
RC
Lee
J H
JH
Walsh
D A
DA
D000818:Animals; D002118:Calcium / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006019:Glycolysis; D009119:Muscle Contraction; D009132:Muscles / Q000201:enzymology*; D006005:Phosphorylases / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology
D003035:Cobalt; D014700:Verapamil; D006005:Phosphorylases; D002118:Calcium