Pharmacological identification of inward current evoked by dopamine in rat subthalamic neurons in vitro

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Abstract

Dopaminergic mechanisms in the subthalamic nucleus (STN) are implicated in the pathophysiology of Parkinson's disease. Here, electrophysiological responses of STN neurons to dopamine (DA) were investigated by using whole-cell patch-clamp recordings in the rat brain slice preparation. Under current-clamp, DA depolarized membrane potential and increased the frequency of spontaneous action potentials of STN neurons. Under voltage-clamp, DA (3-300 μM) produced a reversible concentration-dependent inward current (IDA; 6-40 pA) with an EC50 of 13 μM. This DA-induced current had a negative slope conductance which reversed at -102 mV. It was partially reduced by barium and by superfusion with an elevated concentration of extracellular K+. Moreover, TTX and glutamate receptor antagonists (CNQX and AP5) did not significantly affect the DA responses, indicating that IDA is not dependent upon afferent synaptic activity in the STN. Quinpirole, a D2 receptor agonist, mimicked the DA action more effectively than did the D1 agonist SKF-38393. The D2 antagonist sulpiride, but not the D1 antagonist SCH-23390, blocked responses induced by DA. Intracellular application of G-protein inhibitor GDP-β-S also suppressed IDA. GTP-γ-S, added to the pipette solution, evoked a sustained inward shift in the absence of DA. These results suggest that DA increases the activity of STN neurons via activation of G-protein-coupled D2-like receptors which reduce a K+ conductance.

Original languageEnglish (US)
Pages (from-to)772-781
Number of pages10
JournalNeuropharmacology
Volume42
Issue number6
DOIs
StatePublished - May 27 2002

Keywords

  • Brain slice
  • D2 receptor
  • Dopamine
  • Potassium channel
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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