Nonselective cation channels are essential for maintaining intracellular Ca2+ levels and spontaneous firing activity in the midbrain dopamine neurons.
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.
Kim
Shin Hye
SH
Department of Physiology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong Jangan-ku, Suwon 440-746, Republic of Korea.
Choi
Yu Mi
YM
Jang
Jin Yong
JY
Chung
Sungkwon
S
Kang
Yun Kyung
YK
Park
Myoung Kyu
MK
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
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