Effect of volatile general anesthetics and n-alcohols on glutamate-stimulated increases in calcium ion flux in hippocampal membrane vesicles.

N-Methyl-D-aspartate (NMDA) receptor activity was determined by measurement of L-glutamate-stimulated increases in free intracellular calcium concentrations (Cai) in membrane vesicles isolated from mouse hippocampi. Incubation with anesthetic concentrations of the volatile general anesthetics, halothane, enflurane, and diethyl ether, inhibited NMDA responses. The n-alcohols, ethanol, propanol, butanol and pentanol inhibited NMDA receptor responses, but methanol was ineffective. The ability of volatile anesthetics and n-alcohols to inhibit NMDA responses appears to be unrelated to the ability of some of these agents to increase resting Cai since no correlation occurred between the two effects. The results of this study show that hippocampal NMDA receptors are sensitive to inhibition by volatile general anesthetics and n-alcohols. This effect may, in part, underlie their anesthetic effects in vivo.