Potassium Channel Blockers Inhibit D2 Dopamine, but Not A1Adenosine, Receptor‐Mediated Inhibition of Striatal Dopamine Release

Wayne A. Cass, Nancy R. Zahniser

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Abstract: D2 dopamine autoreceptors and A1 adenosine heteroreceptors inhibit the evoked release of dopamine from rat striatum. We examined the role of potassium channels in this modulation by determining the effects of two potassium channel blockers, 4‐aminopyridine and tetraethylammonium, on the modulation of electrically stimulated release of endogenous dopamine from rat striatal slices. Maximally effective concentrations of the D2 dopamine receptor agonist N‐0437 (10 nM) and of adenosine (50 μM) caused a 30% inhibition of evoked dopamine overflow, and their effects were additive. When coperfused with N‐0437, both 4‐aminopyridine and tetraethylammonium blocked the inhibition caused by N‐0437 in a dose‐dependent manner. 4‐Aminopyridine was approximately three orders of magnitude more potent than tetraethylammonium, with complete blockade occurring at 3μM and 1 mM, respectively. Binding experiments confirmed that neither 4‐aminopyridine nor tetraethylammonium was a direct‐acting D2 dopamine receptor antagonist at the concentration necessary to block the release‐modulatory effect of D2 receptor activation. In contrast, the inhibitory modulation produced by adenosine was not affected by 4‐aminopyridine (30 μM) or tetraethylammonium (1 mM). These results suggest that D2 dopamine and A1 adenosine receptors inhibit dopamine release in the striatum by different mechanisms. D2 dopamine autoreceptor action appears to involve potassium channels, whereas A1 adenosine receptor action does not.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalJournal of Neurochemistry
Issue number1
StatePublished - Jul 1991


  • 4‐Aminopyridine
  • Aadenosine receptor
  • D dopamine receptor
  • Dopamine release
  • Potassium channels
  • Striatum
  • Tetraethylammonium

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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