The Interaction between hAmylin Receptor and Nicotinic Receptors in Rat Cholinergic Basal Forebrain

来源 :BIT`s 3rd Annual World Congress of NeuroTalk-2012(2012第三届国际神 | 被引量 : 0次 | 上传用户:chenshuae9o
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  Regulated secretion of Human Amylin (hAmylin) that is co-released with insulin from pancreatic B-cells and the actions of this peptide on its target tissues maintains cell excitability and glucose homeostasis.Inappropriate control of hAmylin secretion results in human disease, in particular in Alzheimers disease.What receptors are acted by human amylin leads to neurotoxicity in neurons of brain is unknown.Nicotinic acetylcholine receptors (nAChRs) are known to play a critical role in a variety of nervous diseases.In the present study, we sought to determine the inter-relationships between these receptors by examining the actions of hAmylin and nicotine on whole-cell currents and membrane potential in basal forebrain neurons.Whole cell patch-clamp recordings were performed on enzymatically dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus.The results shown hAmylin or nicotine applied individually caused a dose-dependent (lnM-10μM) membrane depolarization and an increase in firing frequency of DBB neurons.Application ofAC253, an amylin receptor antagonist, blocked the excitatory effects of not only hAmylin but also nicotine, Dihydro-beta-erythroidine (DHβE), a non-7nAChR antagonist, blocked the effects of nicotine and also hAmylin.Similar effects were also observed in voltage-clamp mode.Bath application of hAmylin and nicotine resulted in reduction of whole cell currents in a voltage range between-30 and +30 mV.Nicotine and hAmylin depressed the potassium currents.DHBE attenuated the effects of hAmylin and nicotine.These electrophysiological results suggest that hAmylin receptor and nAChRs on DBB neurons are coupled and may function in a co-operative manner to influence the excitability of DBB neurons.These evidences are immensely important to understand the cause and mechanisms of Alzheimers disease.
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