Valérie Itier, University of Geneva, Medical School, Geneva, Switzerland
Daniel Bertrand, University of Geneva, Medical School, Geneva, Switzerland
Published online: September 2005
DOI: 10.1038/npg.els.0005057
Nicotinic receptors are cationic ligand-gated channels that mediate fast synaptic transmission in the peripheral nervous system. Alternative and specific nicotinic receptors are expressed in the central nervous system where they modulate neurotransmitter release.
Keywords: synaptic transmission; neurotransmitter; receptors; brain; ligand-gated channels
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Figure 1. Protein structure of the nicotinic receptors: (a) Alignment of human 4, 2 and 7 polypeptides with exon numbering and splicing positions indicated by the arrows. SP: signal peptide. TM I to TM IV indicate the position of the four transmembrane domains. The open box between the SP and TM1 symbolizes the cysteine loop and the two adjacent cysteines on the 4 and 7 subunits. (b) Schematic three-dimensional representation of the receptor inserted into the membrane (left panel). A top view of a heteromeric receptor with two and three subunits is represented on the right. Second transmembrane domains, which form the walls of the ionic pore, are schematized by filled circles.
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Figure 2. (a) Human karyotype and localization of the known nicotinic receptor genes. Note the 4, 3 and 5 gene cluster on chromosome 15. The position of the 7 and the duplicated 7 exons 5–10 (dup7) are represented on the same chromosome 15. Genes coding for the muscle receptor subunits are localized on chromosomes 2 and 17. (b) Muscle and neuronal gene subunits with their respective positions and accession numbers.
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| References | |
| Bertrand D, Galzi JL, Devillers-Thiery A, Bertrand S and Changeux JP (1993). Stratification of the channel domain in neurotransmitter receptors. Current Opinion in Cell Biology 5: 688–693. | |
| Brejc K, van Dijk WJ, Klaassen RV, et al. (2001) Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411: 269–276. | |
| book Changeux JP (1990) "Functional architecture and dynamics of the nicotinic acetylcholine receptor: an allosteric ligand-gated ion channel". In: Changeux JP, Llinàs RR, Purves D and Bloom FE (eds.) Fidia Research Foundation Neuroscience Award Lectures, pp. 21–168. New York, NY: Raven Press. | |
| Couturier S, Bertrand D, Matter JM, et al. (1990). A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX. Neuron 5: 847–856. | |
| Elgoyhen AB, Johnson DS, Boulter J, Vetter DE and Heinemann S (1994) Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell 79: 705–715. | |
| Gault J, Robinson M, Berger R, et al. (1998) Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 52: 173–185. | |
| Khakh BS, Zhou X, Sydes J, Galligan JJ and Lester HA (2000). State-dependent cross-inhibition between transmitter-gated cation channels. Nature 406: 405–410. | |
| Leonard S and Bertrand D (2001) Neuronal nicotinic receptors: from structure to function. Nicotine and Tobacco Research 3: 203–223. | |
| Miyazawa A, Fujiyoshi Y, Stowell M and Unwin N (1999) Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall. Journal of Molecular Biology 288: 765–786. | |
| Radcliffe KA and Dani JA (1998) Nicotinic stimulation produces multiple forms of increased glutamatergic synaptic transmission. Journal of Neuroscience 18: 7075–7083. | |
| Temburni MK, Blitzblau RC and Jacob MH (2000) Receptor targeting and heterogeneity at interneuronal nicotinic cholinergic synapses in vivo. Journal of Physiology 525(1): 21–29. | |
| Further Reading | |
| Alkondon M, Reinhardt S, Lobron C, et al. (1994) Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. II. The rundown and inward rectification of agonist-elicited whole-cell currents and identification of receptor subunits by in situ hybridization. Journal of Pharmacology and Experimental Therapy 271: 494–506. | |
| Bertrand D and Changeux JP (1995) Nicotinic receptor: an allosteric protein specialized for intercellular communication. Seminars in Neuroscience 7: 75–90. | |
| Dani JA (2001) Overview of nicotinic receptors and their roles in the central nervous system. Biological Psychiatry 49: 166–174. | |
| Le Novere N and Changeux JP (1999) The ligand gated ion channel database. Nucleic Acids Research 27: 340–342. | |
| MacDermott AB, Role LW and Siegelbaum SA (1999). Presynaptic ionotropic receptors and the control of transmitter release. Annual Review of Neuroscience 22: 443–485. | |
| Sargent PB (1993) The diversity of neuronal nicotinic acetylcholine receptors. Annual Review of Neuroscience 16: 403–443. | |
| Wonnacott S (1997) Presynaptic nicotinic ACh receptors. Trends in Neuroscience 20: 92–98. | |
| Web Links | |
| ePath BodyMap. A databank of expression information of human and mouse genes, novel or known, in various tissues or cell types and various timings http://bodymap.ims.u-tokyo.ac.jp | |
| ePath Division of Medical Genetics, University of Geneva. Differential gene expression in trisomy Ts65Dn mouse model of Down syndrome http://medgen.unige.ch/research/ts65dn/index.html | |
| ePath Institut Pasteur Receptors and Cognition Laboratory. Jean-Pierre Changeux and the nicotinic acetylcholine receptors http://www.pasteur.fr/recherche/unites/neubiomol/ | |
| ePath Nicotine and the nervous system. Brief overview of the nicotinic receptors and some of their clinical aspects http://www.geocities.com/CapeCanaveral/2257/nictop.html | |
| ePath NCBI Genes and Disease. Most important web site for the linkage or association of genetic variants and diseases http://www.ncbi.nlm.nih.gov/disease/ | |
| ePath Cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle) (CHRNA1); Locus ID: 1134. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1134 | |
| ePath Cholinergic receptor, nicotinic, alpha polypeptide 7 (CHRNA7); Locus ID: 1139. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1139 | |
| ePath Cholinergic receptor, nicotinic, beta polypeptide 4 (CHRNB4); Locus ID: 1143. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1143 | |
| ePath Cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle) (CHRNA1); MIM number: 100690. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?100690 | |
| ePath Cholinergic receptor, nicotinic, alpha polypeptide 7 (CHRNA7); MIM number: 118511. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?118511 | |
| ePath Cholinergic receptor, nicotinic, beta polypeptide 4 (CHRNB4); MIM number: 118509. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?118509 | |
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