Roles Of Nicotinic Acetylcholine Receptor Î² Subunits In Function Of Human Î±4-Containing Nicotinic Receptors
Naturally expressed nicotinic acetylcholine receptors (nAChR) containing Î±4 subunits (Î±4*-nAChR) in combination with Î²2 subunits (Î±4Î²2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. Î²4 subunits are also richly expressed and colocalize with Î±4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, Î±4Î²4-nAChR also may exist and play important functional roles. In this study, properties were determined of human Î±4Î²2- and Î±4Î²4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human Î±4Î²4-nAChR have âˆ¼4-fold higher amplitude than those mediated via human Î±4Î²2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at Î±4Î²4-nAChR than at Î±4Î²2-nAChR. Cytisine and lobeline serve as full agonists at Î±4Î²4-nAChR but are only partial agonists at Î±4Î²2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional Î±4Î²2- and Î±4Î²4-nAChR. Whole-cell current responses show stronger inward rectification for Î±4Î²2-nAChR than for Î±4Î²4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR Î²2 or Î²4 subunits can combine with Î±4 subunits to generate two forms of Î±4*-nAChR with distinctive physiological and pharmacological features. Diversity in Î±4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence. Â© 2006 The Authors. Journal compilation 2006 The Physiological Society.
Journal of Physiology
Digital Object Identifier (DOI)
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 Î² Subunits In Function Of Human Î±4-Containing Nicotinic Receptors" (2006). Neurobiology. 169.