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Pflugers Arch. 2007 Nov;455(2):309-21. Epub 2007 May 10.

Nonselective cation channels are essential for maintaining intracellular Ca2+ levels and spontaneous firing activity in the midbrain dopamine neurons.

Author information

1
Department of Physiology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong Jangan-ku, Suwon 440-746, Republic of Korea.

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.

PMID:
17492308
DOI:
10.1007/s00424-007-0279-2
[Indexed for MEDLINE]

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