title: Calcium-activated non-selective cation currents are involved in generation of tonic and bursting activity in dopamine neurons of the substantia nigra pars compacta.
abstract: Nigral dopamine neurons are transiently activated by high frequency glutamatergic inputs relaying reward-predicting sensory information. The tonic firing pattern of dopamine cells responds to these inputs with a transient burst of spikes that requires NMDA receptors. Here, we show that NMDA receptor activation further excites the cell by recruiting a calcium-activated non-selective cation current (ICAN) capable of generating a plateau potential. Burst firing in vitro is eliminated after blockade of ICAN with flufenamic acid, 9-phenanthrol, or intracellular BAPTA. ICAN is likely to be mediated by a transient receptor potential (TRP) channel, and RT-PCR was used to confirm expression of TRPM2 and TRPM4mRNA in substantia nigra pars compacta.We propose that ICAN is selectively activated during burst firing to boost NMDA currents and allow plateau potentials. This boost mechanism may render DA cells vulnerable to excitotoxicity.
authors.affiliation: Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Mrejeru
authors.forename: Aguan
authors.initials: A
authors.lastname: Wei
authors.forename: Jan Marino
authors.initials: JM
authors.lastname: Ramirez
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005439:Flufenamic Acid / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010616:Phenanthrenes / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D050053:TRPM Cation Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D002614:Chelating Agents; D007473:Ion Channels; D010616:Phenanthrenes; D016194:Receptors, N-Methyl-D-Aspartate; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse; C476766:TRPM4 protein, mouse; D050051:Transient Receptor Potential Channels; D004533:Egtazic Acid; D005439:Flufenamic Acid; C091375:9-phenanthrol; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D004298:Dopamine