Standard Article

Nicotinic Receptors

  1. Laurine Marger,
  2. Valérie Itier,
  3. Daniel Bertrand

Published Online: 17 FEB 2014

DOI: 10.1002/9780470015902.a0005057.pub2

eLS

eLS

How to Cite

Marger, L., Itier, V. and Bertrand, D. 2014. Nicotinic Receptors. eLS. .

Author Information

  1. HiQScreen, Geneva, Switzerland

  1. Based in part on the previous version of this eLS article ‘Nicotinic Receptors’ (2005) by Valérie Itier and Daniel Bertrand.

Publication History

  1. Published Online: 17 FEB 2014

Abstract

Fast neurotransmission in the central and peripheral nervous systems is mediated by the activity of ligand-gated ion channels. Nicotinic acetylcholine receptors (nAChRs) belong to the family of cation-permeable channels and result from the assembly of five subunits that form both the ligand-binding site and the ionic pore. Sixteen genes encoding for these receptors have been identified in mammals and show differential expression throughout the body. Endogenously activated by ACh, nAChRs are the primary target of nicotine contained in tobacco leaves and mediate its addiction. The use of a partial agonist of nicotinic receptors significantly reduces craving and show good outcomes in smoking cessation. Spontaneous variations occurring in the genes encoding for nAChRs are associated with neurological diseases such as myasthenia gravis, to genetically transmissible epilepsies and to nicotine dependence. Dysfunction of the nAChR transmission is associated with diseases including schizophrenia, autism and neurodegenerative diseases such as Alzheimer's. Small molecules have recently shown beneficial outcomes in Alzheimer disease opening new avenues to treat neurological affections.

Key Concepts:

  • Neurotransmission is mediated by integral membrane proteins and can be subdivided into ligand-gated ion channels and G-coupled proteins.

  • Nicotinic acetylcholine receptors belong to the family of cationic ligand-gated ion channels that comprises four transmembrane domains and result from the assembly of five subunit around an axis of pseudosymmetry.

  • Nicotinic acetylcholine receptors are key players in nicotine addiction and the primary target for this natural alkaloid that is contained in tobacco leaves.

  • Nicotinic acetylcholine receptors at the neuromuscular junction play a determinant role in mediating transmission from the motor nerve to the muscle cell. Impairment of these receptor function leads to myasthenia gravis, which can be decomposed in its most common form to an autoimmune disease and in rarer forms in mutations of one or more genes.

  • Dysfunction of the cholinergic system is associated with cognitive impairment and with neurological diseases such as schizophrenia, autism, genetically transmissible epilepsies and neurodegenerative diseases such as Alzheimer's.

  • The development of small chemical molecules such as the partial agonist varenicline is shown to help in smoking cessation programmes and, more recently, for α7 EVP-6124 in the treatment of Alzheimer disease.

Keywords:

  • synaptic transmission;
  • neurotransmitter;
  • receptors;
  • brain;
  • ligand-gated channels