Nicotinic Acetylcholine Receptors in Neurons

Abstract

Nicotinic acetylcholine receptors are members of a superfamily of ligand‐gated ion channels, all of which play a key role in synaptic transmission throughout the nervous system.

Keywords: ligand‐gated channel; nicotine; nicotine receptor; neurotransmitter; central nervous system; peripheral nervous system

Figure 1.

The diversity of neuronal nAChRs arises from the many possible subunit combinations that form the receptors. (a) The 12 cloned neuronal nAChR subunits are represented in different colours. (b) Many nAChRs are constructed from α and β subunit combinations, with the most common being the α4β2 nAChR in the mammalian brain. (c) Although α8 and α9 are capable of forming homo‐oligomeric nAChRs, α7 forms the most common homo‐oligomeric nAChR in the mammalian brain. (d) More complex subunit combinations are possible, with more than one α and/or more than one β subunit combining to form the nAChR. This example, α4α6β2, is a common nAChR in the midbrain dopamine areas and in the target fields of those midbrain neurons.

Figure 2.

A simplified representation of the general topology of an nAChR subunit. The four membrane‐spanning regions (M1–M4) are separated by extracellular and intracellular loops of varying lengths. Although the external domain is labelled simply as the ligand‐binding region, it possesses sites for agonists, antagonists, ions and other modulators. Likewise, the intracellular domain offers sites for intracellular ligands that can modulate and regulate the nAChR.

Figure 3.

Didactic representations of nAChRs at synaptic locations. (a) Fast nicotinic synaptic transmission is depicted. ACh is released presynaptically and transiently opens postsynaptic nAChRs. (b) Presynaptic nAChRs are schematically represented on the presynaptic bouton, where they can influence the release of neurotransmitter that is present in synaptic vesicles. (c) Preterminal nAChRs are schematically represented on the axon before the synaptic terminal. In this location, nAChRs can mediate a depolarization locally to activate voltage‐dependent channels that can consequently induce neurotransmitter release from the presynaptic terminal.

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Further Reading

Berg DK and Conroy WG (2002) Nicotinic alpha 7 receptors: synaptic options and downstream signaling in neurons. Journal of Neurobiology 53: 512–523.

Bertrand D and Changeux JP (1999) Nicotinic receptor: a prototype of allosteric ligand‐gated ion channels and its possible implications in epilepsy. Advances in Neurology 79: 171–188.

Clementi F, Gotti C and Fornasari D (eds) (2000) Handbook of Experimental Pharmacology, vol. 144: Neuronal Nicotinic Receptors. Berlin: Springer‐Verlag.

Dani JA, Ji D and Zhou FM (2001) Synaptic plasticity and nicotine addiction. Neuron 31: 349–352.

De Biasi M (2002) Nicotinic mechanisms in the autonomic control of organ systems. Journal of Neurobiology 53: 568–579.

Jo YH, Talmage DA and Role LW (2002) Nicotinic receptor‐mediated effects on appetite and food intake. Journal of Neurobiology 53: 618–632.

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Zhou FM, Wilson CJ and Dani JA (2002) Cholinergic interneuron characteristics and nicotinic properties in the striatum. Journal of Neurobiology 53: 590–605.

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Dani, John A, and Lester, Robin AJ(Sep 2005) Nicotinic Acetylcholine Receptors in Neurons. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004064]