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

Pflugers Arch. 2007 Nov;455(2):309-21. doi: 10.1007/s00424-007-0279-2. Epub 2007 May 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Apamin / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Dopamine / metabolism*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Imidazoles / pharmacology
  • Ion Channels / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nifedipine / pharmacology
  • Nimodipine / pharmacology
  • Potassium Channels, Calcium-Activated / drug effects
  • Potassium Channels, Calcium-Activated / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers / pharmacology
  • Substantia Nigra / cytology*
  • Tetrodotoxin / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Imidazoles
  • Ion Channels
  • Potassium Channels, Calcium-Activated
  • Sodium Channel Blockers
  • nonselective cation channel protein, rat
  • Apamin
  • Tetrodotoxin
  • Egtazic Acid
  • Nimodipine
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Nifedipine
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium
  • Dopamine