The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily

Abstract

A critical event in the history of biological chemistry was the chemical identification of the first neurotransmitter receptor, the nicotinic acetylcholine receptor. Disciplines as diverse as electrophysiology, pharmacology, and biochemistry joined together in a unified and rational manner with the common goal of successfully identifying the molecular device that converts a chemical signal into an electrical one in the nervous system. The nicotinic receptor has become the founding father of a broad family of pentameric membrane receptors, paving the way for their identification, including that of the GABA(A) receptors.

FIGURE 1.

Upper, binding method by equilibrium dialysis used for the identification of the nicotinic receptor. Lower, effect of the snake toxin α-BGT on binding of the nicotinic agonist [³H]decamethonium (Deca). This figure has been reprinted from Refs. (lower) and (upper).

FIGURE 2.

Purification of the nAChR by affinity chromatography. This figure has been reprinted from Ref. .

FIGURE 3.

First structural observation of the purified nicotinic receptor proteins from E. electricus (upper) and from purified subsynaptic membrane fragments from T. marmorata (lower). This figure has been reprinted from Ref. .

FIGURE 4.

Minimal four-state model for the allosteric transitions of the nicotinic receptor. CB, competitive (orthosteric) blocker; NCB, noncompetitive (channel) blocker; AM, allosteric modulator; P, phosphorylation site. This figure has been reprinted from Ref. .