title: Nonselective cation channels are essential for maintaining intracellular Ca2+ levels and spontaneous firing activity in the midbrain dopamine neurons.
abstract: Intracellular Ca2+ and Ca2+-permeable ion channels are important in regulating the firing activity and pattern of midbrain dopamine neurons, but the role of Ca2+-permeable nonselective cation channels (NSCCs) on spontaneous firing activity is unclear. Therefore, we investigated how Ca2+-permeable NSCCs modulate spontaneous firing activity and cytosolic Ca2+ concentration ([Ca2+]c) in acutely isolated midbrain dopamine neurons of the rat. Applications of voltage-dependent Ca2+ channels antagonists failed to abolish spontaneous firing activity completely, but they decreased firing rate and [Ca2+]c. However, a blockade of NSCCs by 2-APB or SKF96365 more potently suppressed spontaneous firings with a depolarization of membrane potential and strong decreases in basal [Ca2+]c levels. The depolarization of membrane potentials was attenuated by intracellular dialysis with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). NSCCs blockers inhibited oscillatory potentials and decreased basal [Ca2+]c in the presence of tetrodotoxin. Apamin, a small-conductance Ca2+-activated K+ channel inhibitor, depolarized membrane potentials and enhanced firing rates. From these data, we conclude that NSCCs not only make up the tonic Ca2+ entry pathways to uphold basal [Ca2+]c levels but also contribute to generation of spontaneous firings, thereby regulating spontaneous firing activities of the midbrain dopamine neurons.
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong Jangan-ku, Suwon 440-746, Republic of Korea.
authors.forename: Shin Hye
authors.initials: SH
authors.lastname: Kim
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Choi
authors.forename: Jin Yong
authors.initials: JY
authors.lastname: Jang
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kang
authors.forename: Myoung Kyu
authors.initials: MK
authors.lastname: Park
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D007473:Ion Channels; D024681:Potassium Channels, Calcium-Activated; D026941:Sodium Channel Blockers; C491711:nonselective cation channel protein, rat; D001030:Apamin; D013779:Tetrodotoxin; D004533:Egtazic Acid; D009553:Nimodipine; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D004298:Dopamine