NATIVE CHICK NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS ARE MODULATED BY GENERAL ANESTHETICS

Abstract

S443 INTRODUCTION: Recent studies indicate that nicotinic acetylcholine receptors (nAChRs) in the Central Nervous System (CNS) allow presynaptic regulation of the release of other neurotransmitters [1]. Neuronal nAChRs are also putative sites for the inhibition of synaptic transmission in the CNS and autonomic nervous systems caused by general anesthetics [2]. METHODS: We have studied the effects of the general anesthetic isoflurane on the agonist response of chick nAChRs in Xenopus oocytes expressing: alpha 4 beta 2 or alpha 7 subunits and also on native presynaptic and postsynaptic nAChRs in chick sympathetic neurons. RESULTS: The inhalational anesthetic isoflurane inhibits agonist responses in alpha 4 beta 2 type nAChRs in a clinically used range, with an IC50 of 85 [micro sign]M (27% MAC) and a Hill number of 1.3. The homomeric alpha 7 receptor is insensitive to 640 [micro sign]M isoflurane. The range of isoflurane concentrations used clinically in man is between 50 and 500 micromolar. The native nAChRs in chick sympathetic neurons are inhibited by isoflurane with an IC50 of 248 [micro sign]M and a hill coefficient of 3.2. Presynaptic nAChRs, which are thought to contain the alpha 7 subunit, are differently regulated by isoflurane in the sympathetic nervous system. DISCUSSION: In conclusion, the general anesthetic isoflurane differentially modulates neuronal nAChRs according to subunit composition and neuronal nAChRs appear to be a potential site for some of the pharmacological effects of general anesthetics. Inhibition of synaptic transmission as a result of presynaptic nicotinic inhibition in CNS areas such as hippocampus, thalamus, hypothatlamus, nucleus solitarus may contribute to the effects and side effects of general anesthetics.