{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:43:53Z","timestamp":1781102633903,"version":"3.54.1"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,10,28]]},"abstract":"<jats:p>\n                    We have studied the effect of the cholinergic agonist carbachol on the spontaneous release of glutamate in cultured rat hippocampal cells. Spontaneous excitatory postsynaptic currents (sEPSCs) through glutamatergic \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type channels were recorded by means of the patch-clamp technique. Carbachol increased the frequency of sEPSCs in a concentration-dependent manner. The kinetic properties of the sEPSCs and the amplitude distribution histograms were not affected by carbachol, arguing for a presynaptic site of action. This was confirmed by measuring the turnover of the synaptic vesicular pool by means of the fluorescent dye FM 1\u201343. The carbachol-induced increase in sEPSC frequency was not mimicked by nicotine, but could be blocked by atropine or by pirenzepine, a muscarinic cholinergic receptor subtype M1 antagonist. Intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals recorded with the fluorescent probe Fluo-3 indicated that carbachol transiently increased intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration. Since, however, carbachol still enhanced the sEPSC frequency in bis(2-aminophenoxy)ethane-\n                    <jats:italic>N,N,N\u2032,N\u2032<\/jats:italic>\n                    -tetra-acetate-loaded cells, this effect could not be attributed to the rise in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration. On the other hand, the protein kinase inhibitor staurosporine as well as a down-regulation of protein kinase C by prolonged treatment of the cells with 4\u03b2-phorbol 12-myristate 13-acetate inhibited the carbachol effect. This argues for an involvement of protein kinase C in presynaptic regulation of spontaneous glutamate release. Adenosine, which inhibits synaptic transmission, suppressed the carbachol-induced stimulation of sEPSCs by a G protein-dependent mechanism activated by presynaptic A1-receptors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.22.12224","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"12224-12229","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Muscarinic stimulation of synaptic activity by protein kinase C is inhibited by adenosine in cultured hippocampal\u2009neurons"],"prefix":"10.1073","volume":"94","author":[{"given":"Alexandre","family":"Bouron","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Berne, Friedbuehlstrasse 49, CH-3010 Berne, 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