EFFECTS OF ETHANOL AND OTHER INTOXICANT-ANESTHETICS ON VOLTAGE-DEPENDENT SODIUM-CHANNELS OF BRAIN SYNAPTOSOMES

Abstract

Ethanol, diethylether, halothane and enflurane inhibited the veratridine-dependent uptake of 24Na by synaptosomes isolated from rodent [mouse and rat] brain. The inhibitory action of ethanol was similar for uptake periods of 1-10 s and also was observed with batrachotoxin-stimulated Na uptake, demonstrating an inhibition of Na influx through voltage-dependent channels. The inhibitory action of tetrodotoxin on Na uptake was not altered by ethanol, indicating this site on the Na channel was not altered by ethanol. The action of ethanol was selective for different brain regions and was more potent in inhibiting Na uptake in cortex than in cerebellum. Investigation of the effects of temperature on veratridine-stimulated uptake and ethanol actions demonstrated that an increase in temperature (13.degree.-33.degree. C) decreased both the apparent Kd of veratridine and the Vmax of the uptake. Ethanol decreased the apparent Vmax at all temperatures and decreased the apparent Kd at low (13.degree. and 18.degree. C) but not higher (30.degree. and 33.degree. C) temperatures. An increase in temperature mimicked some, but not all, of the effects of ethanol. The disordering of membrane lipids by ethanol and other intoxicant-anesthetic drugs is an important factor in the inhibition of Na channel function by these drugs.