Nicotinic acetylcholine receptors containing α7 subunits on rat cortical neurons do not undergo long-lasting inactivation even when up-regulated by chronic nicotine exposure
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作者:
Kawai, H
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Univ Calif San Diego, Div Biol, Neurobiol Sect, La Jolla, CA 92093 USAUniv Calif San Diego, Div Biol, Neurobiol Sect, La Jolla, CA 92093 USA
Kawai, H
[1
]
Berg, DK
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Univ Calif San Diego, Div Biol, Neurobiol Sect, La Jolla, CA 92093 USAUniv Calif San Diego, Div Biol, Neurobiol Sect, La Jolla, CA 92093 USA
Berg, DK
[1
]
机构:
[1] Univ Calif San Diego, Div Biol, Neurobiol Sect, La Jolla, CA 92093 USA
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.