Nonselective cation channels are essential for maintaining intracellular Ca super(2+) levels and spontaneous firing activity in the midbrain dopamine neurons

• Published in: Pflügers Archiv 2007-11, Vol.455 (2), p.309-321
• Main Authors: Kim, Shin Hye, Choi, Yu Mi, Jang, Jin Yong, Chung, Sungkwon, Kang, Yun Kyung, Park, Myoung Kyu
• Format: Article
• Language: English
• Subjects: Antagonists
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-007-0279-2

Intracellular Ca super(2+) and Ca super(2+)-permeable ion channels are important in regulating the firing activity and pattern of midbrain dopamine neurons, but the role of Ca super(2+)-permeable nonselective cation channels (NSCCs) on spontaneous firing activity is unclear. Therefore, we investigated how Ca super(2+)-permeable NSCCs modulate spontaneous firing activity and cytosolic Ca super(2+) concentration ([Ca super(2+)] sub(c)) in acutely isolated midbrain dopamine neurons of the rat. Applications of voltage-dependent Ca super(2+) channels antagonists failed to abolish spontaneous firing activity completely, but they decreased firing rate and [Ca super(2+)] sub(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 [Ca super(2+)] sub(c) levels. The depolarization of membrane potentials was attenuated by intracellular dialysis with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tet raacetic acid (BAPTA). NSCCs blockers inhibited oscillatory potentials and decreased basal [Ca super(2+)] sub(c) in the presence of tetrodotoxin. Apamin, a small-conductance Ca super(2+)-activated K super(+) channel inhibitor, depolarized membrane potentials and enhanced firing rates. From these data, we conclude that NSCCs not only make up the tonic Ca super(2+) entry pathways to uphold basal [Ca super(2+)] sub(c) levels but also contribute to generation of spontaneous firings, thereby regulating spontaneous firing activities of the midbrain dopamine neurons.