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*Columbia College, Hunter College High School, and Department of Anesthesiology, Columbia University, New York, New York
Address correspondence to Pamela Flood, MD, Department of Anesthesiology, Columbia University, 630 W. 168th St., New York, NY 10032. Address e-mail to pdf3{at}columbia.edu Reprints will not be available from the authors.
In previous studies we and others have demonstrated that the activation of nicotinic acetylcholine receptors (nAChRs) is inhibited by subanesthetic concentrations of volatile anesthetics. The mechanism by which activation is inhibited is unknown. Studies of the evolutionarily related nAChRs from the electric fish Torpedo have suggested that volatile anesthetics alter the affinity of the agonist for the receptor. We studied the effect of two volatile anesthetics, isoflurane and sevoflurane, on equilibrium binding of the high-affinity nicotinic agonist epibatidine to nicotinic receptors from mouse brain. We studied binding to male and female brain separately, because sex differences in nicotine responses have been reported. Male and female brains have equal epibatidine binding without anesthetic. Isoflurane and sevoflurane reduce the binding of [3H]epibatidine to male and female nicotinic receptors, but only at concentrations at and above those required for anesthesia. The 50% inhibitory concentration for isoflurane inhibition of [3H]epibatidine binding to male brain was 0.58 ± 0.07 mM and to female brain was 1.62 ± 0.30 mM. The 50% inhibitory concentration for sevoflurane inhibition of [3H]epibatidine binding to male brain was 0.77 ± 0.05 mM and to female brain was 0.77 ± 0.04 mM. There was no statistically significant difference in the effect of either drug between sexes (P > 0.05). Although there is a slight decrease in agonist affinity at anesthetic concentrations, the marked reductions in nAChR function at subanesthetic concentrations cannot be attributed to changes in agonist affinity.
IMPLICATIONS: Volatile anesthetics reduce the activation of nicotinic acetylcholine receptors by an unknown mechanism. We have demonstrated that although isoflurane and sevoflurane inhibit agonist affinity, the concentrations required are too large to be responsible for the dynamic changes observed.
This article has been cited by other articles:
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  Z. Xie, B. E. Herring, and A. P. Fox Excitatory and Inhibitory Actions of Isoflurane in Bovine Chromaffin Cells J Neurophysiol, December 1, 2006; 96(6): 3042 - 3050. [Abstract] [Full Text] [PDF]
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 V. Fodale, L. B. Santamaria, S. B. Backman, and G. Plourde Different actions of sevoflurane and propofol on central nicotinic receptors may explain differences in hypnotic antagonism by cholinesterase inhibitors Br. J. Anaesth., May 1, 2004; 92(5): 773 - 775. [Full Text] [PDF]
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