Nicotinic acetylcholine receptors containing α7 subunits on rat cortical neurons do not undergo long-lasting inactivation even when up-regulated by chronic nicotine exposure

被引:95
作者
Kawai, H [1 ]
Berg, DK [1 ]
机构
[1] Univ Calif San Diego, Div Biol, Neurobiol Sect, La Jolla, CA 92093 USA
关键词
alpha; 7; bungarotoxin; inactivation; nicotinic; receptor; up-regulation;
D O I
10.1046/j.1471-4159.2001.00526.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chronic exposure to (-)nicotine has been widely reported to up-regulate nicotinic acetylcholine receptors on neurons and induce long-term inactivation as a possible cause. Nicotinic receptors containing alpha7 subunits are among the most abundant in brain and influence diverse cellular events. Whole-cell patch clamp recording from embryonic rat cortical neurons in culture was used to identify responses from alpha7-containing receptors. Immunochemical staining for glutamic acid decarboxylase (GAD) indicated that both GABAergic and non-GABAergic neurons expressed the receptors. Exposure to micromolar concentrations of nicotine for 1-4 days caused up-regulation of the receptors as measured by [alpha-I-125]-bungarotoxin binding. Carbachol produced the same up-regulation, and cell counts demonstrated that neuronal survival was unchanged. The up-regulation was accompanied by an increased whole-cell response; no evidence was found for long-lasting inactivation. Autonomic alpha7-containing receptors also avoided long-lasting inactivation, even though the receptors were down-regulated by nicotine, Blocking protein synthesis or protein glycosylation prevented receptor up-regulation on cortical neurons, suggesting that new synthesis was required. No evidence was found for a preexisting intracellular pool that supplied receptors to the surface. The results indicate that alpha7-containing receptors differ from other receptor subtypes in their regulation by nicotine and demonstrate further that long-lasting inactivation is not an obligatory requirement for up-regulation in this case.
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页码:1367 / 1378
页数:12
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