Volatile anesthetics inhibit dihydropyridine binding to malignant hyperthermia-susceptible and normal pig skeletal muscle membranes

BACKGROUND: Surface membrane dihydropyridine receptor Ca2+ channels may play a role in the response of malignant hyperthermia-susceptible skeletal muscle to volatile anesthetics. METHODS: We determined the effect of halothane, enflurane, and isoflurane on the binding of the Ca2+ channel blocker PN200-110 to skeletal muscle membranes isolated from malignant hyperthermia-susceptible and normal pigs. RESULTS: In the presence of 0.4 mM halothane, the maximal [3H]PN200-110 binding to both normal and malignant hyperthermia membranes was reduced by 37-43% (P < 0.05). There was no difference in the equilibrium constant for the halothane-dependent inhibition of [3H]PN200-110 binding to these two types of membranes. There also was no significant difference among halothane, enflurane, or isoflurane in their ability to inhibit [3H]PN200-110 binding to either normal or malignant hyperthermia membranes. CONCLUSIONS: Volatile anesthetics inhibit the binding of PN200-110 to skeletal muscle membranes by decreasing the number of functionally active dihydropyridine receptor proteins. This inhibition is similar for membranes isolated from both normal and malignant hyperthermia-susceptible muscle, thus providing no evidence for a halothane-induced functional defect in this protein in malignant hyperthermia-susceptible muscle. However, the results of this study also indicate that the mechanism by which volatile anesthetics decrease surface membrane Ca2+ currents in skeletal muscle is by reducing the number of functional dihydropyridine receptor Ca2+ channels.