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 degrees 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 less than 0.005). Nonlinear regression analysis fit of the binding data indicates halothane produced a 48% decrease (P less than 0.05) in the maximal number of binding sites (Bmax) with no effect on the dissociation constant (Kd). As voltage-dependent Ca2+ channels are important in mediating neurotransmission, the marked decrease in channel number (Bmax) associated with halothane exposure suggests that this phenomenon might be related to the mechanism of general anesthesia.
Drenger
B
B
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.
Heitmiller
E S
ES
Quigg
M
M
Blanck
T J
TJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000378:metabolism*; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology; D017275:Isradipine; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane; D017275:Isradipine