W-7, a calmodulin antagonist, and contracture of malignant hyperthermia susceptible skeletal muscle.
1. In malignant hyperthermia susceptible muscle fibers, the calmodulin antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%) induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene sodium (6 microM) prevented and reversed W-7 induced contracture: nifedipine did not. 3. In chemically skinned fibers, 10 microM, 1.0 microM, and 0.1 microM W-7 released 100%, 30%, and 10% of stored calcium respectively, and the effect of 10 microM W-7 was irreversible in that the SR was unable to re-sequestor calcium after exposure to the drug. 4. The release of calcium by W-7 was not prevented by exogenously added calmodulin (3 microM), nor mimicked by mastoparan (10 microM). 5. Calcium release by W-7 appears to be independent of calmodulin inhibition.
Holland
M
M
Virginia-Maryland Regional College of Veterinary Medicine, VA.
Williams
J H
JH
Lee
J C
JC
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D004357:Drug Synergism; D006221:Halothane / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D010455:Peptides; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D014862:Wasp Venoms / Q000494:pharmacology
D002147:Calmodulin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D013449:Sulfonamides; D014862:Wasp Venoms; D002110:Caffeine; C017967:W 7; C037500:mastoparan; D003620:Dantrolene; D002118:Calcium; D006221:Halothane