Roles Of Nicotinic Acetylcholine Receptor β Subunits In Function Of Human α4-Containing Nicotinic Receptors
Department
neurobiology
Document Type
Article
Abstract
Naturally expressed nicotinic acetylcholine receptors (nAChR) containing α4 subunits (α4*-nAChR) in combination with β2 subunits (α4β2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. β4 subunits are also richly expressed and colocalize with α4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, α4β4-nAChR also may exist and play important functional roles. In this study, properties were determined of human α4β2- and α4β4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human α4β4-nAChR have ∼4-fold higher amplitude than those mediated via human α4β2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at α4β4-nAChR than at α4β2-nAChR. Cytisine and lobeline serve as full agonists at α4β4-nAChR but are only partial agonists at α4β2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional α4β2- and α4β4-nAChR. Whole-cell current responses show stronger inward rectification for α4β2-nAChR than for α4β4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR β2 or β4 subunits can combine with α4 subunits to generate two forms of α4*-nAChR with distinctive physiological and pharmacological features. Diversity in α4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence. © 2006 The Authors. Journal compilation 2006 The Physiological Society.
Publication Date
10-1-2006
Publication Title
Journal of Physiology
ISSN
00223751
Volume
576
Issue
1
First Page
103
Last Page
118
Digital Object Identifier (DOI)
10.1113/jphysiol.2006.114645
Recommended Citation
Wu, Jie; Liu, Qiang; Yu, Kewei; Hu, Jun; Kuo, Yen Ping; Segerberg, Marsha; St, Paul A.; and Lukas, Ronald J., "Roles Of Nicotinic Acetylcholine Receptor β Subunits In Function Of Human α4-Containing Nicotinic Receptors" (2006). Translational Neuroscience. 169.
https://scholar.barrowneuro.org/neurobiology/169