Adenosine receptor expression and modulation of Ca2+ channels in rat striatal cholinergic interneurons

Wen Jie Song, Tatiana Tkatch, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Adenosine is a potent regulator of acetylcholine release in the striatum, yet the mechanisms mediating this regulation are largely undefined. To begin to fill this gap, adenosine receptor expression and coupling to voltage-dependent Ca2+ channels were studied in cholinergic interneurons by combined whole cell voltage-clamp recording and single-cell reverse transcription-polymerase chain reaction. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. Nearly all of these interneurons (90%, n = 28) expressed detectable levels of A1 adenosine receptor mRNA. A(2a) and A(2b) receptor mRNAs were less frequently detected. A3 receptor mRNA was undetectable. Adenosine rapidly and reversibly reduced N-type Ca2+ currents in cholinergic interneurons. The A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine completely blocked the effect of adenosine. The IC50 of the A1 receptor selective agonist 2-chloro-N6- cyclopentyladenosine was 45 nM, whereas it was near 30 μM for the A(2a) receptor agonist CGS-21680. Dialysis with GDPβS or brief exposure to the G protein (G(i/o)) alkylating agent N-ethylmaleimide also blocked the adenosine modulation. The reduction in N-type currents was partially reversed by depolarizing prepulses. A membrane-delimited pathway mediated the modulation, because it was not seen in cell-attached patches when agonist was applied to the bath. Activation of protein kinase C attenuated the adenosine modulation. Taken together, our results argue that activation of A1 adenosine receptors in cholinergic interneurons reduces N-type Ca2+ currents via a membrane- delimited, G(i/o) class G-protein pathway that is regulated by protein kinase C. These observations establish a cellular mechanism by which adenosine may serve to reduce acetylcholine release.

Original languageEnglish (US)
Pages (from-to)322-332
Number of pages11
JournalJournal of neurophysiology
Volume83
Issue number1
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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