title: Muscarine activates the sodium-calcium exchanger via M receptors in basal forebrain neurons.
abstract: Neurons of the medial septum/diagonal band of Broca (MSDB) project to the hippocampus. Muscarinic cholinergic mechanisms within the MSDB are potent modulators of hippocampal functions; intraseptal scopolamine disrupts and intraseptal carbachol facilitates hippocampus-dependent learning and memory tasks, and the associated hippocampal theta rhythm. In earlier work, we demonstrated that, within the MSDB, the septohippocampal GABAergic but not cholinergic neurons are the primary target of muscarinic manipulations and that muscarinic activation of septohippocampal GABAergic neurons is mediated directly via M(3) receptors. In the present study, we examined the ionic mechanism(s) underlying the excitatory actions of muscarine in these neurons. Using whole-cell patch-clamp recording techniques in rat brain slices, we demonstrated that M(3) receptor-mediated muscarinic activation of MSDB neurons is dependent on external Na(+) and is also reduced by bath-applied Ni(2+) and KB-R7943 as well as by replacing external Na(+) with Li(+), suggesting a primary involvement of the Na(+)-Ca(2+) exchanger. We conclude that the M(3) receptor-mediated muscarinic activation of MSDB septohippocampal GABA-type neurons, that is important for cognitive functioning, is mediated via activation of the Na(+)-Ca(2+) exchanger.
authors.affiliation: Department of Psychiatry, CMHC 335A, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Elena
authors.initials: E
authors.lastname: Morozova
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Alreja
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D001711:Biotransformation / Q000187:drug effects; D020667:Diagonal Band of Broca / Q000378:metabolism; D004158:Diphenylacetic Acids / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007477:Ions / Q000378:metabolism; D018021:Lithium Chloride / Q000378:metabolism; D008297:Male; D009116:Muscarine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000187:drug effects*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D004158:Diphenylacetic Acids; D007473:Ion Channels; D007477:Ions; D018721:Muscarinic Agonists; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D019831:Sodium-Calcium Exchanger; C074183:N-(2-chloroethyl)-4-piperidinyl diphenylacetate; D009116:Muscarine; D018021:Lithium Chloride; D013890:Thiourea