Nomenclature: β4

Family: Nicotinic acetylcholine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 498 15q24 CHRNB4 cholinergic receptor, nicotinic, beta 4 (neuronal) 7
Mouse 4 495 9 B Chrnb4 cholinergic receptor, nicotinic, beta polypeptide 4 3
Rat 4 495 8q24 Chrnb4 cholinergic receptor, nicotinic, beta 4 (neuronal) 2
Previous and Unofficial Names
cholinergic receptor, nicotinic, beta polypeptide 4
acetylcholine receptor, nicotinic, beta 4 (neuronal)
Acetylcholine receptor beta 4
N-alpha 2
cholinergic receptor, nicotinic, beta 4
neuronal acetylcholine receptor non-alpha-2 chain
neuronal acetylcholine receptor subunit beta-4
Acrb-4
Acrb4
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
acetylcholine
Tissue Distribution
Brain: medial habenula, mitral cell layer and the accessory olfactory bulb, interpeduncular nucleus, inferior colliculus and the medial vestibular nucleus (mRNA restricted to relatively few nuclei).
Expression level:  High
Species:  Mouse
Technique:  Radioligand binding
References:  13
Brain: medial habenula, cerebral cortex, hippocampus, motor trigeminal nucleus, locus coreulus, cerebellum, interpeduncular nucleus (no expression in thalamus).
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  2
Tissue Distribution Comments
Deletion of β4 subunit in knockout mice has little effect on total [3H]- or [125I]-epibatidine binding with the exception of a partial reduction in the signal intensity in the fasiculus retroflexus, interpeduncular nucleus and the inferior colliculus. The effects of β4 gene deletion were more readily observable when cytisine was included in the incubation with [3H]- or [125I]-epibatidine. Under these experimental conditions, robust effects could be observed in the medial habenula, the fasiculus retroflexis, the interpeducular nucleus and the inferior colliculus, all of which expressed high levels of cytisine-resistant [125I]epibatidine binding [1,10].

Expression of β4 mRNA in rhesus monkey (Macaca Mulatta) brain is similar to that described in rodents. High expression is detected in thalamic nuclei, substantia nigra pars compacta and vertral tegmental area. Expression is also detected in cortex (layer VI showing the highest level of expression) and lower levles in hippocampus and caudate [4].

Expression of β4 mRNA in suirrel monkey (Samimiri sciureus) appears to differ from that in rodents or macaques. High levels of expression brain have been detected in caudate, putamen and hippocampus. However, compared to expression levels in the cotex, levels of expression were relatively low in thalamic nuclei, substantia nigra pars compacta and medial habenula [6].
Physiological Consequences of Altering Gene Expression
Knockout mice display reduced acetylcholine-activated whole-cell currents in superior cervical ganglion neurons; autonomic cardiac and intestinal dysfunction are also observed; decreased anxiety-related responses; resistance to nicotine-induced seizures; decreased nicotine withdrawal. Expression of α3 subunit mRNA is greatly reduced in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of β4 knockout mice.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  5,9,11-12,14
Clinically-Relevant Mutations and Pathophysiology
Disease:  Sporadic amyotrophic lateral sclerosis
OMIM:  105400
References:  8
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human multiple 8

REFERENCES

1. Baddick CG, Marks MJ. (2011) An auroradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants. Biochem. Pharmacol.,, . [PMID:21575611]

2. Duvoisin RM, Deneris ES, Patrick J, Heinemann S. (1989) The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4. Neuron3 (4): 487-96. [PMID:2642007]

3. Eng CM, Kozak CA, Beaudet AL, Zoghbi HY. (1991) Mapping of multiple subunits of the neuronal nicotinic acetylcholine receptor to chromosome 15 in man and chromosome 9 in mouse. Genomics9 (2): 278-82. [PMID:2004777]

4. Han ZY, Le Novère N, Zoli M, Hill JA, Champtiaux N, Changeux JP. (2000) Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur. J. Neurosci.12 (10): 3664-74. [PMID:11029636]

5. Kedmi M, Beaudet AL, Orr-Urtreger A. (2004) Mice lacking neuronal nicotinic acetylcholine receptor beta4-subunit and mice lacking both alpha5- and beta4-subunits are highly resistant to nicotine-induced seizures. Physiol. Genomics17 (2): 221-9. [PMID:14996991]

6. Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW. (2000) Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J. Comp. Neurol.425 (1): 58-69. [PMID:10940942]

7. Raimondi E, Rubboli F, Moralli D, Chini B, Fornasari D, Tarroni P, De Carli L, Clementi F. (1992) Chromosomal localization and physical linkage of the genes encoding the human alpha 3, alpha 5, and beta 4 neuronal nicotinic receptor subunits. Genomics12 (4): 849-50. [PMID:1572664]

8. Sabatelli M, Eusebi F, Al-Chalabi A, Conte A, Madia F, Luigetti M, Mancuso I, Limatola C, Trettel F, Sobrero F et al.. (2009) Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum. Mol. Genet.18 (20): 3997-4006. [PMID:19628475]

9. Salas R, Cook KD, Bassetto L, De Biasi M. (2004) The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology47 (3): 401-7. [PMID:15275829]

10. Salas R, Pieri F, De Biasi M. (2004) Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit. J. Neurosci.24 (45): 10035-9. [PMID:15537871]

11. Salas R, Pieri F, Fung B, Dani JA, De Biasi M. (2003) Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor. J. Neurosci.23 (15): 6255-63. [PMID:12867510]

12. Wang N, Orr-Urtreger A, Chapman J, Rabinowitz R, Korczyn AD. (2003) Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction. Mol. Pharmacol.63 (3): 574-80. [PMID:12606764]

13. Whiteaker P, Jimenez M, McIntosh JM, Collins AC, Marks MJ. (2000) Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine. Br. J. Pharmacol.131 (4): 729-39. [PMID:11030722]

14. Xu C, Lu Y, Tang G, Wang R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am. J. Physiol.277 (5 Pt 1): G1055-63. [PMID:10564112]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: β4. Last modified on 14/03/2014. Accessed on 30/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=474.

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