title: Enhancement of excitatory postsynaptic potentials by preceding application of acetylcholine in mesencephalic dopamine neurons.
abstract: Previously, we reported that Ca(2+) influx through nicotinic acetylcholine (ACh) receptors (nAChRs) activates a fulfenamic acid (FFA)-sensitive inward current, presumably a Ca(2+)-activated nonselective cation current (I(CAN)), in mesencephalic dopamine (DA) neurons. This current exhibited a negative slope conductance in the voltage range between -80 and -40mV and its activation led to a dramatic change in the responses to a transient application of glutamate, from single spikes to burst discharges. In this study, to examine the effect of activation of the FFA-sensitive current on EPSPs, we applied ACh (1mM) by transient air pressure shortly before electrical stimulation to evoke EPSPs in DA neurons. Application of ACh enhanced the amplitude of EPSPs when it preceded the electrical stimulation by less than 2 s, but not when the interval was longer than 3 s. In addition, this enhancement was critically dependent on intracellular Ca(2+) and the membrane potentials of the postsynaptic cell. Furthermore, the enhancing effect of ACh on EPSPs was sensitive to FFA and phenytoin. These results suggest that Ca(2+) influx caused by cholinergic inputs enhances EPSPs via activation of the FFA- and phenytoin-sensitive current.
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: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D037342:Pertussis Toxin / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D062367:ortho-Aminobenzoates; D004533:Egtazic Acid; D010672:Phenytoin; D019284:Thapsigargin; C022838:nickel chloride; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D001285:Atropine; D009532:Nickel; D037342:Pertussis Toxin; D014633:Valine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000109:Acetylcholine; D004298:Dopamine