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

Zi Tao Zhu, Ke Zhong Shen, Steven W. Johnson

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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
Issue number6
StatePublished - 2002
Externally publishedYes


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

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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