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.