PMID:12606764

Citation	Wang, N, Orr-Urtreger, A, Chapman, J, Rabinowitz, R and Korczyn, AD (2003) Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction. Mol. Pharmacol. 63:574-80
Abstract	Neuronal nicotinic acetylcholine receptors (nAChR) are composed of 12 subunits (alpha 2-alpha 10 and beta 2-beta 4), which play the central role in autonomic transmission. beta 4 subunits are abundantly expressed in autonomic ganglia, forming acetylcholine binding sites and ion channels with alpha 3 or alpha 3 and alpha 5 subunits as pentameric receptors. To investigate the physiological and pharmacological properties of beta 4 subunits in autonomic ganglia, we measured autonomic functions in knockout mice lacking nAChR subunit beta 4 (beta 4(-/-)) and wild-type mice. beta 4(-/-) mice had an attenuated bradycardiac response to high frequency (60 pulse/s) vagal stimulation, as well as an increased sensitivity to hexamethonium blockade at low dose (3 mg/kg) and a reduced ileal contractile response to the nicotinic agonists cytisine, dimethylphenylpiperazinium iodide, nicotine (10 mg/kg each), and epibatidine (0.1 mg/kg). The results suggest that beta 4 subunits are important components of nAChRs in autonomic ganglia. Deficiency of beta 4 subunits altered ion channel properties, conductance, and sensitivity and affinity of receptors to agonists and antagonists, affecting ganglionic transmission.
Links	PubMed
Keywords	Acetylcholine/metabolism; Animals; Aortic Bodies/metabolism; Disease Models, Animal; Ganglia, Autonomic/metabolism; Ganglionic Blockers/pharmacology; Heart Diseases/metabolism; Heart Function Tests; Hexamethonium/pharmacology; Ileal Diseases/metabolism; Mice; Mice, Knockout; Protein Subunits/deficiency; Protein Subunits/metabolism; Receptors, Nicotinic/deficiency; Receptors, Nicotinic/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ACHB4		GO:0051971: positive regulation of transmission of nerve impulse	ECO:0000315:		P		Figure 2 suggests the B4 subunit of nAchR helps transmit nerve impulses. At low concentrations, the ganglionic blocker C6 prevents transmission of vagal stimulation in KO mice. WT mice however still receive the transmission of the nerve impulse, suggesting B4 subunit of nAchR is involved in transmissions of nerve impulses. The authors state "the bradycardic effect was significantly attenuated in β4−/− mice." Thus, the subunit must maintain the extent of a nerve pulse.	complete CACAO 9239
MOUSE:ACHB4	involved_in	GO:0051971: positive regulation of transmission of nerve impulse	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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