title: Fulfenamic acid sensitive, Ca(2+)-dependent inward current induced by nicotinic acetylcholine receptors in dopamine neurons.
abstract: Nicotinic acetylcholine receptors (nAChRs) exhibit high Ca(2+) permeabilities and the Ca(2+)-influx through the nAChRs may be involved in regulation of a variety of signal processing in the postsynaptic neurons. The mesencephalic dopamine (DA) neurons receive cholinergic inputs from the brainstem and express abundant nAChRs. Here we report that the Ca(2+)-influx induced by a transient pressure application of ACh activates an inward current mediated by nAChRs and subsequently an inward current component that is sensitive to fulfenamic acid (FFA) and phenytoin, presumably a Ca(2+)-activated nonselective cation current in the DA neurons in the midbrain slices of the rat. The FFA- and phenytoin-sensitive current exhibits a negative slope conductance below -40 mV, suggesting its role in significant enhancement of depolarizing responses. In the current clamp recordings with perforated patch clamp configuration, bath application of carbachol markedly enhanced the glutamate-induced depolarization, which led to a long-lasting depolarizing hump. Activation of nAChRs is involved in this process, in cooperation with muscarinic receptors that suppress afterhyperpolarization caused by Ca(2+)-activated K(+)-channels. The long-lasting depolarizing hump was suppressed by FFA. All these results suggested a potential role of the FFA-sensitive current triggered by nAChR activation in marked enhancement of the excitatory synaptic response in DA neurons.
authors.affiliation: Department of Integrative Physiology, National Institute for Physiological Sciences and Graduate University for Advanced Studies, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamashita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Isa
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D005439:Flufenamic Acid / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008464:Mecamylamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D012717:Sesquiterpenes / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D002614:Chelating Agents; D002712:Chlorides; D018679:Cholinergic Agonists; D007783:Lactones; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012717:Sesquiterpenes; D018698:Glutamic Acid; D004533:Egtazic Acid; D005439:Flufenamic Acid; D010672:Phenytoin; C046319:thapsigargicin; D008464:Mecamylamine; D001285:Atropine; D002217:Carbachol; C013411:biocytin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D008239:Lysine; C081124:acetyl chloride; D002118:Calcium; D004298:Dopamine