Depression of calcium channel blocker binding to rat brain membranes by halothane

The present study evaluates the action of volatile anesthetics on the voltage-dependent Ca²⁺ channels in isolated rat brain membranes, measured as changes in binding of the Ca²⁺ channel blocker [³H]isradipine to these membranes. Equilibrium binding studies with increasing concentrations of [³H]isradipine (0.01-1 nM) in the presence of halothane (1.9%), isoflurane (2.3%), and enflurane (4.8%) at 25°C were performed. Only halothane produced a significant depression in the specific binding of isradipine to the brain membranes at 0.5 and 1.0 nM [³H]isradipine (P = 0.028 and 0.018, respectively). Isoflurane and enflurane had such inconsistent effects that the data were inconclusive. Halothane produced a significant dose-dependent inhibition of binding, the maximum inhibition being 44% (P < 0.005). Nonlinear regression analysis fit of the binding data indicates halothane produced a 48% decrease (P < 0.05) in the maximal number of binding sites (B(max)) with no effect on the dissociation constant (K(d)). As voltage-dependent Ca²⁺ channels are important in mediating neurotransmission, the marked decrease in channel number (B(max)) associated with halothane exposure suggests that this phenomenon might be related to the mechanism of general anesthesia.