{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:02:10Z","timestamp":1773666130248,"version":"3.50.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,8,1]]},"abstract":"<jats:p>The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency was investigated in single ventricular cardiomyocytes isolated from guinea pig hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37 degrees C with the whole-cell patch clamp method, under K(+)-free conditions. A comparison is made between the response to frequency changes for ICa in the basal state and after the application of drugs which elevate the level of adenosine-3',5'-cyclic monophosphate (cAMP) within the cells. Peak basal ICa was reduced with an increase in stimulation rate from 0.5 Hz to 1, 2, 3, 4, or 5 Hz. This frequency-induced reduction of ICa was enhanced by reduced temperature, was unchanged when Na+ or Ba2+ carried the basal Ca2+ channel current, and was greatly enhanced after elevating cAMP levels with forskolin, isoprenaline, or 8-(4-chlorophenylthio)-cyclic AMP. We examined the mechanism of the enhancement of the frequency-induced reduction of ICa by cAMP, and found two conditions which abolished it: (a) application of isoprenaline when Na+ carried the Ca2+ channel current in Ca(2+)-free solution, or (b) application of 3-isobutyl-1-methylxanthine, a broad-spectrum phosphodiesterase inhibitor. It was further shown that an elevation of both ICa and cAMP (induced by isoprenaline), and not an increase of ICa alone (induced by Bay K 8644), is required to produce the extra component of reduction by frequency. It is concluded that Ca2+ entry results in feedback regulation of ICa, through the activation of Ca(2+)-dependent phosphodiesterase(s). This is important in the context of sympathetic stimulation, which produces the companion conditions of an elevated heart rate and increases in cAMP levels and Ca2+ entry.<\/jats:p>","DOI":"10.1085\/jgp.106.2.175","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T23:51:34Z","timestamp":1084492294000},"page":"175-201","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes."],"prefix":"10.1085","volume":"106","author":[{"given":"S P","family":"Kaspar","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D J","family":"Pelzer","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1995,8,1]]},"container-title":["The Journal of general physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/106\/2\/175\/1768668\/175.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/106\/2\/175\/1768668\/175.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T11:01:40Z","timestamp":1690369300000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/106\/2\/175\/26442\/Modulation-by-stimulation-rate-of-basal-and-cAMP"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,8,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.106.2.175","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,8,1]]}}}