Calmodulin-antagonist drugs and porcine malignant hyperpyrexia.
1. Landrace swine were identified as malignant hyperpyrexia susceptible (MHS) or control by the contracture responses of gracilis muscle fibre bundles to 3% halothane, 2 mmol/l caffeine and 80 mmol/l KCl. The effects of calmodulin-antagonist drugs on the contractile behaviour of control and MHS preparations were investigated in vitro. 2. Calmodulin-antagonists at micromolar concentrations induced contracture in both control and MHS muscle. Pretreatment of MHS muscle with calmodulin-antagonist drugs potentiated its response to halothane and caffeine. 3. These results suggest that calmodulin-antagonist drugs cause an increase in myoplasmic Ca2+ concentration in both control and MHS muscle.
Collins
S P
SP
Department of Medicine and Clinical Science, John Curtin School of Medical Research, Australian National University, Canberra.
White
M D
MD
Denborough
M A
MA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000503:physiopathology*; D010640:Phenothiazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine
D002147:Calmodulin; D010640:Phenothiazines; D002110:Caffeine; D011189:Potassium Chloride; D006221:Halothane