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Journal of Neuroscience, Vol 16, 2592-2604, Copyright © 1996 by Society for Neuroscience
Muscarinic (m2/m4) receptors reduce N- and P-type Ca2+ currents in rat neostriatal cholinergic interneurons through a fast, membrane- delimited, G-protein pathway
Z Yan and DJ Surmeier
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, 38163, USA.
The signaling pathways mediating the muscarinic modulation of Ca2+ currents
in neostriatal cholinergic interneurons were studied by combined
patch-clamp recording and single-cell reverse transcription- PCR.
Cholinergic interneurons were identified by the presence of choline
acetyltransferase mRNA. These neurons expressed Q-, N-, L-, P-, and R-type
Ca2+ currents and the mRNA for the alpha1 subunits believed to form the
channels underlying these currents (classes A, B, C, D, and E). Of the
interneurons tested, nearly all expressed M2-class (m2, m4) receptor mRNAs,
whereas m1 receptor mRNA was found in only a subset (approximately 30%) of
the sample. The muscarinic agonist oxotremorine methiodide produced a
dose-dependent reduction of N- and P-type Ba2+ currents through Ca2+
channels that was antagonized by atropine. N- ethylmaleimide eliminated the
modulation, as did preincubation with pertussis toxin. The onset and offset
of the modulation were rapid and dose-dependent. The modulation was also
attenuated by strong depolarizing prepulses and was not observed in
cell-attached membrane patches. Taken together, our results suggest that
activation of M2- class muscarinic receptors in cholinergic interneurons
reduces N- and P- type Ca2+ currents through a membrane-delimited pathway
using a Gi/o- class G-protein. This signaling pathway provides a cellular
mechanism for hetero- and homosynaptic control of interneuronal activity
and acetylcholine release in the striatum.
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