Gene Symbol: Chrna3
Description: cholinergic receptor nicotinic alpha 3 subunit
Alias: neuronal acetylcholine receptor subunit alpha-3, Acetylcholine receptor alpha 3 (neuronal nicotine), acetylcholine receptor alpha3, cetylcholine receptor alpha 3 (neuronal nicotine), cholinergic receptor nicotinic alpha polypeptide 4, cholinergic receptor, nicotinic, alpha 3 (neuronal), cholinergic receptor, nicotinic, alpha polypeptide 3
Species: rat
Products:     Chrna3

Top Publications

  1. Boulter J, Connolly J, Deneris E, Goldman D, Heinemann S, Patrick J. Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family. Proc Natl Acad Sci U S A. 1987;84:7763-7 pubmed
    ..These results indicate that the alpha 3, alpha 4, and beta 2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system. ..
  2. Dvorakova M, Lips K, Brüggmann D, Slavikova J, Kuncova J, Kummer W. Developmental changes in the expression of nicotinic acetylcholine receptor alpha-subunits in the rat heart. Cell Tissue Res. 2005;319:201-9 pubmed
    ..Our results indicate an additional non-neuronal expression of nAChR subunits in the rat heart that, as in skeletal muscle, precedes functional innervation and then undergoes changes in its distribution on the surface of cells. ..
  3. Yu W, Guan Z, Nordberg A. Postnatal upregulation of alpha4 and alpha3 nicotinic receptor subunits in the brain of alpha7 nicotinic receptor-deficient mice. Neuroscience. 2007;146:1618-28 pubmed
    ..These data suggest that increased levels of alpha4, alpha3-containing nAChRs, co-assembled with the alpha5 nAChR subunit, may contribute to the normal brain development of alpha7 -/- and alpha7 +/- mice. ..
  4. Grailhe R, de Carvalho L, Paas Y, Le Poupon C, Soudant M, Bregestovski P, et al. Distinct subcellular targeting of fluorescent nicotinic alpha 3 beta 4 and serotoninergic 5-HT3A receptors in hippocampal neurons. Eur J Neurosci. 2004;19:855-62 pubmed
    ..Taken together, the fluorescent and electrophysiological studies presented here demonstrate the predominant intracellular location of alpha3beta4-nACh receptors and the predominant expression of the 5-HT3AR in dendritic surface loci. ..
  5. De Biasi M, Nigro F, Xu W. Nicotinic acetylcholine receptors in the autonomic control of bladder function. Eur J Pharmacol. 2000;393:137-40 pubmed
    ..These findings suggest that nicotinic receptors containing the alpha(3) and the beta(4) subunits are necessary for normal bladder function. ..
  6. Del Signore A, Gotti C, Rizzo A, Moretti M, Paggi P. Nicotinic acetylcholine receptor subtypes in the rat sympathetic ganglion: pharmacological characterization, subcellular distribution and effect of pre- and postganglionic nerve crush. J Neuropathol Exp Neurol. 2004;63:138-50 pubmed
    ..This observation and the lack of any effect of preganglionic nerve crush on the number of nicotinic receptors suggest that the peripheral targets affect the organization of intraganglionic synapses in adult SCG. ..
  7. Luo S, Zhangsun D, Schroeder C, Zhu X, Hu Y, Wu Y, et al. A novel ?4/7-conotoxin LvIA from Conus lividus that selectively blocks ?3?2 vs. ?6/?3?2?3 nicotinic acetylcholine receptors. FASEB J. 2014;28:1842-53 pubmed publisher
    ..4/7-CTx LvIA is a new, potent, selective ?3?2 nAChR antagonist, which will enable detailed studies of ?3?2 nAChR structure, function, and physiological roles...
  8. Lev Lehman E, Bercovich D, Xu W, Stockton D, Beaudet A. Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and CHRNB4. J Hum Genet. 2001;46:362-6 pubmed
    ..disease families and controls identified numerous genetic variants, including high-frequency polymorphisms in both CHRNA3 and CHRNB4...
  9. Vincler M, Eisenach J. Plasticity of spinal nicotinic acetylcholine receptors following spinal nerve ligation. Neurosci Res. 2004;48:139-45 pubmed
    ..We propose that the increased expression of the alpha3 and alpha5 nicotinic subunits may contribute to the mechanical hypersensitivity observed following spinal nerve ligation. ..

More Information


  1. Lindovský J, Kaniaková M, Svobodová L, Vyskocil F, Krusek J. Role of negatively charged amino acids in beta 4 F-loop in activation and desensitization of alpha 3 beta 4 rat neuronal nicotinic receptors. Biochim Biophys Acta. 2008;1778:864-71 pubmed publisher
    ..The double mutation substantially accelerated the return from long-term desensitization induced by Epi. ..
  2. Teng Y, Rezvani K, De Biasi M. UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP. Biochem Pharmacol. 2015;97:518-530 pubmed publisher
    ..Overall,we identify CHIP as an E3 ligase for α3 and UBXN2A as a protein that may efficiently regulate the stability of CHIP's client substrates. ..
  3. Adams M, Nikkel A, Donnelly Roberts D, Watt A, Johnston J, Cowsert L, et al. In vitro and in vivo effects of an alpha3 neuronal nicotinic acetylcholine receptor antisense oligonucleotide. Brain Res Mol Brain Res. 2004;129:67-79 pubmed
    ..Results of our studies suggest that Isis 106567 may be a useful in vivo tool for characterizing the functional significance of alpha3 expression in the CNS. ..
  4. Nieves Cintrón M, Caballero Rivera D, SILVA W, Navedo M, Lasalde Dominicci J. Functional contribution of alpha3L8' to the neuronal nicotinic alpha3 receptor. J Neurosci Res. 2008;86:2884-94 pubmed publisher
    ..These data demonstrate that structural alterations at position alpha3L8' could propagate to the agonist-binding site. ..
  5. Elliott K, Ellis S, Berckhan K, Urrutia A, Chavez Noriega L, Johnson E, et al. Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits. J Mol Neurosci. 1996;7:217-28 pubmed
  6. Bansal A, Singer J, Hwang B, Xu W, Beaudet A, Feller M. Mice lacking specific nicotinic acetylcholine receptor subunits exhibit dramatically altered spontaneous activity patterns and reveal a limited role for retinal waves in forming ON and OFF circuits in the inner retina. J Neurosci. 2000;20:7672-81 pubmed
    ..These results indicate that retinal waves mediated by nAChRs are involved in, but not required for, the development of neural circuits that define the ON and OFF sublamina of the inner plexiform layer. ..
  7. Chen H, Su C. Endogenous activation of nicotinic receptors underlies sympathetic tone generation in neonatal rat spinal cord in vitro. Neuropharmacology. 2006;51:1120-8 pubmed
    ..Nicotinic activation of glycinergic and GABAergic interneurons may provide a recurrent inhibition of SPNs for homeostatic regulation of sympathetic outflow. ..
  8. Lomazzo E, MacArthur L, Yasuda R, Wolfe B, Kellar K. Quantitative analysis of the heteromeric neuronal nicotinic receptors in the rat hippocampus. J Neurochem. 2010;115:625-34 pubmed publisher
    ..Results suggested these subtypes have comparable binding affinities for the nicotinic ligands used here. ..
  9. Hone A, Ruiz M, Scadden M, Christensen S, Gajewiak J, Azam L, et al. Positional scanning mutagenesis of ?-conotoxin PeIA identifies critical residues that confer potency and selectivity for ?6/?3?2?3 and ?3?2 nicotinic acetylcholine receptors. J Biol Chem. 2013;288:25428-39 pubmed publisher
    ..The results of these studies provide molecular insights into designing ligands that selectively target ?6?2* nAChRs. ..
  10. Wu C, Lee R, Chen P, Tsai A, Chen M, Kuo J, et al. L-type calcium channels in sympathetic ?3?2-nAChR-mediated cerebral nitrergic neurogenic vasodilation. Acta Physiol (Oxf). 2014;211:544-58 pubmed publisher
    ..This calcium influx causes noradrenaline release, initiating sympathetic-parasympathetic (axo-axonal) interaction-induced nitrergic dilation of porcine basilar arteries. ..
  11. Spies M, Lips K, Kurzen H, Kummer W, Haberberger R. Nicotinic acetylcholine receptors containing subunits alpha3 and alpha5 in rat nociceptive dorsal root ganglion neurons. J Mol Neurosci. 2006;30:55-6 pubmed
    ..2004; Papadopolou et al., 2004). To this end, calcium-imaging and double-labeling immunofluorescence with nAChR alpha-subunit-specific antibodies, in combination with markers for nociceptive neurons (TRPV1, I-B4), were applied. ..
  12. Srivatsan M, Treece J, Shotts E. Nicotine alters nicotinic receptor subunit levels differently in developing Mammalian sympathetic neurons. Ann N Y Acad Sci. 2006;1074:505-13 pubmed
  13. Zhang X, Albers K, Gold M. Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat. Neuroscience. 2015;284:483-99 pubmed publisher
  14. Virginio C, Graziani F, Terstappen G. Differential inhibition of rat alpha3* and alpha7 nicotinic acetylcholine receptors by tetrandrine and closely related bis-benzylisoquinoline derivatives. Neurosci Lett. 2005;381:299-304 pubmed
    ..The different potencies and multiple modes of action on nAChRs may help to better understand the pharmacology of these receptors and to aid in novel drug design. ..
  15. Rassadi S, Krishnaswamy A, Pié B, McConnell R, Jacob M, Cooper E. A null mutation for the alpha3 nicotinic acetylcholine (ACh) receptor gene abolishes fast synaptic activity in sympathetic ganglia and reveals that ACh output from developing preganglionic terminals is regulated in an activity-dependent retrograde ma. J Neurosci. 2005;25:8555-66 pubmed
  16. Boulter J, Evans K, Goldman D, Martin G, Treco D, Heinemann S, et al. Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor alpha-subunit. Nature. 1986;319:368-74 pubmed
  17. Xiao Y, Kellar K. The comparative pharmacology and up-regulation of rat neuronal nicotinic receptor subtype binding sites stably expressed in transfected mammalian cells. J Pharmacol Exp Ther. 2004;310:98-107 pubmed
  18. Verbois S, Scheff S, Pauly J. Time-dependent changes in rat brain cholinergic receptor expression after experimental brain injury. J Neurotrauma. 2002;19:1569-85 pubmed
    ..Persistent deficits in alpha7* nAChr expression following TBI may contribute to impaired functional outcome following brain injury. ..
  19. Albuquerque E, Pereira E, Alkondon M, Rogers S. Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev. 2009;89:73-120 pubmed publisher
    ..Despite these numerous developments, our understanding of the contributions of specific neuronal nAChR subtypes to the many facets of physiology throughout the body remains in its infancy. ..
  20. Yang X, McDonough J, Fyodorov D, Morris M, Wang F, Deneris E. Characterization of an acetylcholine receptor alpha 3 gene promoter and its activation by the POU domain factor SCIP/Tst-1. J Biol Chem. 1994;269:10252-64 pubmed
    ..These results lead us to propose that alpha 3 activation by SCIP/Tst-1 is achieved via protein-protein interactions between SCIP/Tst-1 and a specific complement of transcription factors that act directly on the promoter. ..
  21. Xu W, Gelber S, Orr Urtreger A, Armstrong D, Lewis R, Ou C, et al. Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A. 1999;96:5746-51 pubmed
    ..The phenotype in -/- mice may be similar to the rare human genetic disorder of megacystis-microcolon-intestinal hypoperistalsis syndrome...
  22. Voitenko L, Voitenko S, Skok M, Purnyn H, Skok V. Nicotinic acetylcholine receptor subtypes in rat superior cervical ganglion neurons as studied by sequential application of two alpha-subunit-specific antibodies. Neurosci Lett. 2001;303:37-40 pubmed
  23. Shan K, Qi X, Long Y, Nordberg A, Guan Z. Decreased nicotinic receptors in PC12 cells and rat brains influenced by fluoride toxicity--a mechanism relating to a damage at the level in post-transcription of the receptor genes. Toxicology. 2004;200:169-77 pubmed
    ..The results suggest that the deficit of nAChRs induced by fluoride toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress. ..
  24. Dutertre S, Nicke A, Lewis R. Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic acetylcholine receptor. J Biol Chem. 2005;280:30460-8 pubmed
  25. Grady S, Moretti M, Zoli M, Marks M, Zanardi A, Pucci L, et al. Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the alpha3beta4* and alpha3beta3beta4* subtypes mediate acetylcholine release. J Neurosci. 2009;29:2272-82 pubmed publisher
  26. Colón Sáez J, Yakel J. The ?7 nicotinic acetylcholine receptor function in hippocampal neurons is regulated by the lipid composition of the plasma membrane. J Physiol. 2011;589:3163-74 pubmed publisher
    ..These data provide new insights into themechanism of desensitization of ?7 nAChRs by providing evidence that the lipid composition of the plasma membrane can modulate the activity of the ?7 nAChRs. ..
  27. Di Angelantonio S, Matteoni C, Fabbretti E, Nistri A. Molecular biology and electrophysiology of neuronal nicotinic receptors of rat chromaffin cells. Eur J Neurosci. 2003;17:2313-22 pubmed
  28. Marritt A, Cox B, Yasuda R, McIntosh J, Xiao Y, Wolfe B, et al. Nicotinic cholinergic receptors in the rat retina: simple and mixed heteromeric subtypes. Mol Pharmacol. 2005;68:1656-68 pubmed
  29. Perry D, Xiao Y, Nguyen H, Musachio J, Dávila García M, Kellar K. Measuring nicotinic receptors with characteristics of alpha4beta2, alpha3beta2 and alpha3beta4 subtypes in rat tissues by autoradiography. J Neurochem. 2002;82:468-81 pubmed
  30. Cesa L, Higgins C, Sando S, Kuo D, Levandoski M. Specificity determinants of allosteric modulation in the neuronal nicotinic acetylcholine receptor: a fine line between inhibition and potentiation. Mol Pharmacol. 2012;81:239-49 pubmed publisher
    ..Our work has implications for rational drug design for nicotinic receptors and sheds light on mechanisms of allosteric modulation in nAChRs, especially the subtle differences between potentiation and inhibition. ..
  31. Whiteaker P, Peterson C, Xu W, McIntosh J, Paylor R, Beaudet A, et al. Involvement of the alpha3 subunit in central nicotinic binding populations. J Neurosci. 2002;22:2522-9 pubmed
    ..However, widespread but lower levels of alpha3-independent -resistant [125I]epibatidine binding were also seen. Again, this may indicate the existence of an additional, minor population of non-alpha3 -resistant sites. ..
  32. Salas R, Cook K, Bassetto L, De Biasi M. The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology. 2004;47:401-7 pubmed
    ..mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion. ..
  33. Berrettini W, Yuan X, Tozzi F, Song K, Francks C, Chilcoat H, et al. Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry. 2008;13:368-73 pubmed publisher
    ..In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5))...