ALPHA-4-BETA-2 NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS IN THE CENTRAL-NERVOUS-SYSTEM ARE INHIBITED BY ISOFLURANE AND PROPOFOL, BUT ALPHA-7-TYPE NICOTINIC ACETYLCHOLINE-RECEPTORS ARE UNAFFECTED

Background The mechanisms of action of general anesthetics are not com pletely understood. Many general anesthetics are reported to potentiat e gamma-aminobutyric acid (GABA(A)) and glycine receptors in the centr al nervous system (CNS) and to inhibit the muscle-type nicotinic acety lcholine receptor (nAChR). The effects of general anesthetics on anoth er family of ligand-gated ion channel in the CNS, the nAChRs, have not been defined. Methods: Two types of CNS acetylcholine receptor, the a lpha 4 beta 2 receptor or the alpha 7 homomeric receptor, were express ed heterologously in Xenopus laevis oocytes. Using the standard two-mi croelectrode voltage-clamp technique, peak acetylcholine-gated current was measured before and after coapplication of isoflurane or propofol . Results: Coapplication of either isoflurane or propofol with acetylc holine resulted in potent, dose-dependent inhibition of the alpha 4 be ta 2 receptor current with median inhibitory concentrations of 85 and 19 mu M, respectively. The inhibition of the alpha 4 beta 2 receptor b y both isoflurane and propofol appears to be com petitive with respect to acetylcholine. The alpha 7 receptor current was not effected by ei ther anesthetic. Conclusions: The CNS-type nAChRs are differentially a ffected by isoflurane and propofol. The alpha 4 beta 2 receptor is aff ected by isoflurane more potently than the most sensitive GABA,or glyc ine receptor that has been reported, whereas the alpha 7 homomeric rec eptor is not affected by either anesthetic. Inhibition of specific sub types of nAChRs in the CNS, along with potentiation of GABA(A) and gly cine receptors, may contribute to the effects and side effects of gene ral anesthetics.