Adenosine Receptor Expression And Modulation Of Ca2+ Channels In Rat Striatal Cholinergic Interneurons. Wen-Jie Song, Tatiana Tkatch and D. James Surmeier. Department of Physiology and Institute for Neuroscience, Northwestern University Medical School, Chicago, IL.
APStracts 6:0486N, 1999.
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 RT-PCR. 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. A2a and A2b 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 CPT completely blocked the effect of adenosine. The IC50 of the A1 receptor selective agonist CCPA was 45 nM, whereas it was near 30 µM for the A2a receptor agonist CGS-21680. Dialysis with GDP?S or brief exposure to the G protein (Gi/o) alkylating agent N-ethylmaleimide also blocked the adenosine modulation. The reduction in N-type currents was partially reversed by depolarizing pre-pulses. A membrane-delimited pathway mediated the modulation, as 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, Gi/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.
Received 5 February 1999; accepted in final form 2 September 1999.
APS Manuscript Number J085-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999