Effect of diltiazem, verapamil and dantrolene on the contractility of isolated malignant hyperpyrexia-susceptible human skeletal muscle.
1. Diltiazem (10 mumol/L) and verapamil (10 mumol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures. 2. Like the skeletal muscle relaxant dantrolene sodium (6 mumol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine. 3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive. 4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca2+ influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome. 5. These results also suggest an abnormality in transverse tubule-sarcoplasmic reticulum communication.
Foster
P S
PS
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Hopkinson
K C
KC
Denborough
M A
MA
D002110:Caffeine / Q000037:antagonists & inhibitors; D003620:Dantrolene / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004198:Disease Susceptibility; D006221:Halothane / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology*
D002110:Caffeine; D011189:Potassium Chloride; D014700:Verapamil; D004110:Diltiazem; D003620:Dantrolene; D006221:Halothane