Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons

doi:10.1113/jphysiol.2008.162743

	Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons
	Yang, Kechun 1,2; Hu, Jun 2; Lucero, Linda 3; Liu, Qiang 2; Zheng, Chao 2; Zhen, Xuechu 1; Jin, Guozhang1 ; Lukas, Ronald J.3; Wu, Jie 2
刊名	JOURNAL OF PHYSIOLOGY-LONDON
	2009-01-15
卷号	587 期号:2 页码:345-361
ISSN号	0022-3751
DOI	10.1113/jphysiol.2008.162743
文献子类	Article
英文摘要	Dopaminergic (DAergic) neuronal activity in the ventral tegmental area (VTA) is thought to contribute generally to pleasure, reward, and drug reinforcement and has been implicated in nicotine dependence. nAChRs expressed in the VTA exhibit diverse subunit compositions, but the functional and pharmacological properties are largely unknown. Here, using patch-clamp recordings in single DAergic neurons freshly dissociated from rat VTA, we clarified three functional subtypes of nAChRs (termed ID, IID and IIID receptors) based on whole-cell current kinetics and pharmacology. Kinetic analysis demonstrated that comparing to ID, IID receptor-mediated current had faster activation and decay constant and IIID receptor-mediated current had larger current density. Pharmacologically, ID receptor-mediated current was sensitive to the alpha 4 beta 2-nAChR agonist RJR-2403 and antagonist dihydro-beta-erythroidine (DH beta E); IID receptor-mediated current was sensitive to the selective alpha 7-nAChR agonist choline and antagonist methyllycaconitine (MLA); while IIID receptor-mediated current was sensitive to the beta 4-containing nAChR agonist cytisine and antagonist mecamylamine (MEC). The agonist concentration-response relationships demonstrated that IID receptor-mediated current exhibited the highest EC50 value compared to ID and IIID receptors, suggesting a relatively low agonist affinity of type IID receptors. These results suggest that the type ID, IID and IIID nAChR-mediated currents are predominately mediated by activation of alpha 4 beta 2-nAChR, alpha 7-nAChR and a novel nAChR subtype(s), respectively. Collectively, these findings indicate that the VTA DAergic neurons express diversity and multiplicity of functional nAChR subtypes. Interestingly, each DAergic neuron predominantly expresses only one particularly functional nAChR subtype, which may have distinct but important roles in regulation of VTA DA neuronal function, DA transmission and nicotine dependence.
资助项目	Arizona Biomedical Research Commission[0028] ; Arizona Biomedical Research Commission[0057] ; Institute for Mental Health Research, and Philip Morris International through their External Research Program[00000000] ; Barrow Neurological Foundation[00000000] ; National Institutes of Health[NS40417] ; National Institutes of Health[DA15389]
WOS关键词	SUBUNIT MESSENGER-RNAS ; 4 BETA 2 ; NUCLEUS-ACCUMBENS ; PHARMACOLOGICAL CHARACTERIZATION ; HIPPOCAMPAL-NEURONS ; SUBSTANTIA-NIGRA ; PATCH-CLAMP ; ADDICTION ; ACTIVATION ; DIVERSITY
WOS研究方向	Neurosciences & Neurology ; Physiology
语种	英语
出版者	WILEY
WOS记录号	WOS:000262488200008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279342]
专题	院士及顾问专家
通讯作者	Wu, Jie
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China 2.St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA; 3.St Josephs Hosp, Barrow Neurol Inst, Div Neurobiol, Phoenix, AZ 85013 USA;
推荐引用方式 GB/T 7714	Yang, Kechun,Hu, Jun,Lucero, Linda,et al. Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons[J]. JOURNAL OF PHYSIOLOGY-LONDON,2009,587(2):345-361.
APA	Yang, Kechun.,Hu, Jun.,Lucero, Linda.,Liu, Qiang.,Zheng, Chao.,...&Wu, Jie.(2009).Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons.JOURNAL OF PHYSIOLOGY-LONDON,587(2),345-361.
MLA	Yang, Kechun,et al."Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons".JOURNAL OF PHYSIOLOGY-LONDON 587.2(2009):345-361.