EFFECTS OF HALOTHANE ON THE NICOTINIC ACETYLCHOLINE-RECEPTOR FROM TORPEDO-CALIFORNICA

To determine whether the binding of anesthetics to key membrane receptors is a plausible mode of action, we modeled the effect of the general anesthetic halothane in the nicotinic acetylcholine receptor membrane system isolated from Torpedo californica. Our results demonstrated that halothane inhibits the binding of [H-3]phencyclidine ([H-3]PCP) to the acetylcholine receptor. The inhibition was reversible, concentration dependent, and had an equilibrium dissociation constant (K-d) of 2.2% atm halothane at 25 degrees. Double-reciprocal plots of the halothane effects at Various phencyclidine (PCP) concentrations imply that, under equilibrium conditions, halothane inhibits [H-3]PCP binding competitively. In contrast, results from kinetic studies showed that the rate of PCP dissociation is highly sensitive to halothane with EC(50) = 0.8% atm halothane in nitrogen. Several possible interpretations are discussed; however, the basic observation was that the kinetics of [H-3]PCP binding to the nicotinic acetylcholine receptor was affected by halothane at low concentrations in this model system.