Acetylcholine Receptors

BOUZAT C; CHRESTIA, J.F.

Textbook of Ion Channels.

CRC Press

Año: 2023;

The nicotinic receptor (nAChR) is the prototype of the Cys-loop receptor family of pentameric ligand-gated ion channels. It operates as a near perfect on-off switch that responds to ACh by rapidly opening its ion channel. Thus, nAChRs are involved in chemical synapses and are key actors in vital physiological processes throughout the animal kingdom. In vertebrates, they comprise a family of ACh-activated cation channels widely distributed in the central and peripheric nervous system and in non-neuronal cells. They mediate skeletal muscle contraction, autonomic responses, and exert a large modulatory influence in the brain, where they contribute to cognitive processes and regulate behaviors. The wide structural and functional diversity of nAChRs as well as their main modulatory roles in the nervous system have kindled interest as potential therapeutic targets for a large spectrum of medical conditions and have inspired the development of selective ligands and discovery drug programs.This chapter provides insights into the molecular function of the nAChR and the structural and mechanistic basis of channel activation and drug modulation and illustrates how structural and mechanistic differences among nAChR subtypes translate into significant physiological differences and how nAChRs are currently exploited as therapeutic drug targets.