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Research ArticleArticle

Deficiency of Nicotinic Acetylcholine Receptor β4 Subunit Causes Autonomic Cardiac and Intestinal Dysfunction

Ningshan Wang, Avi Orr-Urtreger, Joab Chapman, Ruth Rabinowitz and Amos D. Korczyn
Molecular Pharmacology March 2003, 63 (3) 574-580; DOI: https://doi.org/10.1124/mol.63.3.574
Ningshan Wang
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Avi Orr-Urtreger
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Joab Chapman
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Ruth Rabinowitz
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Amos D. Korczyn
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Abstract

Neuronal nicotinic acetylcholine receptors (nAChR) are composed of 12 subunits (α2–α10 and β2–β4), which play the central role in autonomic transmission. β4 subunits are abundantly expressed in autonomic ganglia, forming acetylcholine binding sites and ion channels with α3 or α3 and α5 subunits as pentameric receptors. To investigate the physiological and pharmacological properties of β4 subunits in autonomic ganglia, we measured autonomic functions in knockout mice lacking nAChR subunit β4 (β4−/−) and wild-type mice. β4−/− 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 β4 subunits are important components of nAChRs in autonomic ganglia. Deficiency of β4 subunits altered ion channel properties, conductance, and sensitivity and affinity of receptors to agonists and antagonists, affecting ganglionic transmission.

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Molecular Pharmacology: 63 (3)
Molecular Pharmacology
Vol. 63, Issue 3
1 Mar 2003
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Research ArticleArticle

Deficiency of Nicotinic Acetylcholine Receptor β4 Subunit Causes Autonomic Cardiac and Intestinal Dysfunction

Ningshan Wang, Avi Orr-Urtreger, Joab Chapman, Ruth Rabinowitz and Amos D. Korczyn
Molecular Pharmacology March 1, 2003, 63 (3) 574-580; DOI: https://doi.org/10.1124/mol.63.3.574

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Research ArticleArticle

Deficiency of Nicotinic Acetylcholine Receptor β4 Subunit Causes Autonomic Cardiac and Intestinal Dysfunction

Ningshan Wang, Avi Orr-Urtreger, Joab Chapman, Ruth Rabinowitz and Amos D. Korczyn
Molecular Pharmacology March 1, 2003, 63 (3) 574-580; DOI: https://doi.org/10.1124/mol.63.3.574
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