Molecular Pharmacology, Vol 20, 498-505, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Allosteric Effects of Volatile Anesthetics on the Membrane-Bound Acetylcholine Receptor Protein

I. Stabilization of the High-Affinity State

¹ Department of Biological Chemistry, School of Medicine, and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90024

The volatile anesthetics halothane, chloroform, and ether preferentially stabilize the membrane-bound acetylcholine receptor protein prepared from the marine ray Torpedo californica in a conformational form which binds agonists with high affinity. Since these anesthetics do not require the presence of the cationic ligand to facilitate the transition from the low-affinity state to the high-affinity state, these agents can be considered as positive heterotropic effectors of the acetylcholine receptor protein. Aliphatic alcohols, which have well-defined physiological effects at neuromuscular junctions, also stabilize the high-affinity form of the acetylcholine receptor protein in vitro. The effectiveness of the primary alcohols and the anesthetics in stabilizing the tightly binding form correlates with their respective membrane/buffer partition coefficients, emphasizing the importance of these perturbants’ hydrophobicity in altering the structure of this membrane-bound protein. If the high-affinity form of the receptor protein is the manifestation in vitro of the desensitized receptor in vivo, this heterotropic effect could explain the depression of synaptic transmission by volatile anesthetics. By increasing the concentration of desensitized or refractory receptors at crucial central nervous system synapses, volatile anesthetics could block depolarization of postsynaptic membranes by neurotransmitters.

This article has been cited by other articles:

				J. Changeux, A Devillers-Thiery, and P Chemouilli Acetylcholine receptor: an allosteric protein Science, September 21, 1984; 225(4668): 1335 - 1345. [Abstract] [PDF]