Open AccessDepression of Calcium Channel Blocker Binding to Rat Brain Membranes by Halothane
Author(s) -
Benjamin Drenger,
Eugenie S. Heitmiller,
Mary Quigg,
Thomas J. J. Blanck
Publication year - 1992
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/00000539-199205000-00023
Subject(s) - halothane , isradipine , isoflurane , medicine , enflurane , dissociation constant , anesthesia , membrane , calcium channel blocker , pharmacology , biophysics , calcium , endocrinology , biochemistry , receptor , chemistry , dihydropyridine , biology
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.