ISOFLURANE AND SEVOFLURANE INTERACT WITH THE NICOTINIC ACETYLCHOLINE-RECEPTOR CHANNELS IN MICROMOLAR CONCENTRATIONS

Background: This study was performed to elucidate and compare the effe cts of sevoflurane and of isoflurane on the nicotinic acetylcholine re ceptor of mouse myotubes, The experiments mere done with special refer ence to anesthetic concentrations considerably less than those used fo r clinical anesthesia. Methods: The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-dri ven liquid filament switch was used for the ultrafast application of a cetylcholine alone or in combination with isoflurane or sevoflurane. I n addition, the patches were preexposed to either anesthetic, precedin g the activation with acetylcholine. Results: The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhib ition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane . At higher concentrations of sevoflurane, the current decay became bi exponential, In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations. Conc lusion: At the nicotinic acetylcholine receptor, isoflurane and sevofl urane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and le ss than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.