BACKGROUND This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for 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-driven liquid filament switch was used for the ultrafast application of acetylcholine alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding 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 inhibition 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 biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations. CONCLUSIONS At the nicotinic acetylcholine receptor, isoflurane and sevoflurane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and less than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.