Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a super-family of Cysloop ligand-gated ion channels that respond to endogenous acetylcholine (ACh) or other cholinergic ligands. These receptors are also the targets of drugs such as nicotine (the main addictive agent delivered by cigarette smoke) and are involved in a variety of physiological and pathophysiological processes. Numerous studies have shown that the expression and/or function of nAChRs is compromised in many neurological and psychiatric diseases. Furthermore, recent studies have shown that neuronal nAChRs are found in a large number of nonneuronal cell types including endothelial cells, glia, immune cells, lung epithelia and cancer cells where they regulate cell differentiation, proliferation and inflammatory responses. The aim of this review is to describe the most recent findings concerning the structure and function of native nAChRs inside and outside the nervous system.

Keywords: Neuronal nicotinic acetylcholine receptor subtypes; knockout and knockout in mice; ligand binding site; nonneuronal nicotinic acetylcholine receptors; stochiometry; subunit composition..

Fig. (1)

The structure of neuronal nicotinic acetylcholine receptors. A: Structure showing the arrangement of nAChR subunits and the location of the two ACh-binding sites. B) A section of the nAChR with the five subunits arranged around a central cation-conducting pore. C) A single nAChR subunit embedded in the membrane. The extracellular amino acid terminal portion is followed by three hydrophobic transmembrane domains (M1-M3), a large intracellular loop, and a fourth hydrophobic transmembrane domain (M4). The transmembrane M2 segments lining the ion path wall are shown in dark grey.

Fig. (2)

The pentameric arrangement of nAChR subunits in an (α4)3(β2)2 subtype (left) and α7 homopentameric subtype (right). The localisations of the subunit interfaces of the orthosteric binding sites are indicated, together with the primary component P(+) carried by the α subunits and the complementary component C(-)carried by α or non-α subunit. The subunits that may occupy an accessory position are also indicated. In addition to the two orthosteric sites, the (α4)3(β2)2 subtype has a binding site at the α4α4 interface (star).