{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T07:46:48Z","timestamp":1698306408846},"reference-count":0,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[1995,5,1]],"date-time":"1995-05-01T00:00:00Z","timestamp":799286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[1995,5]]},"abstract":"<jats:p>The facilitation of L\u2010type Ca2+ current (ICa), which sometimes occurs with an increase in stimulation frequency, was investigated in single guinea\u2010pig ventricular cardiomyocytes using whole\u2010cell recording and K(+)\u2010free solutions. With a holding potential of \u201080 mV, an increase in frequency from 0.5 to 1, 2, 3 or 4 Hz caused either a small or large initial reduction, or a transient enhancement (facilitation) of peak ICa, which developed rapidly and was followed by a reduction of ICa. Reducing the frequency to 0.1 or 0.2 Hz caused a depression of ICa on the first pulse that was followed by a slower increment. Transient facilitation and depression were entirely absent when either Ba2+ or Na+ was used as the charge carrier in Ca(2+)\u2010free solutions. High concentrations of isoprenaline (1\u20103 microM), forskolin (1\u20103 microM), or 8\u2010(4\u2010chlorophenylthio)\u2010cAMP (150 microM) suppressed but did not abolish the incidence and size of facilitation; employing a holding potential of \u201040 mV also suppressed the incidence of ICa facilitation. Lower isoprenaline concentrations (0.1 and 0.3 microM) greatly enhanced the incidence and magnitude of the transient facilitation occurring with an increase in stimulation rate, but did not diminish the magnitude of the ensuing reduction. When facilitation occurred with 0.1 mM EGTA in the dialysate, or the usual 5 mM EGTA with 0.01 microM extracellular isoprenaline, it developed more slowly after an increase in frequency. In the presence of the phosphodiesterase inhibitor 3\u2010isobutyl\u20101\u2010methylxanthine, an increase in stimulation rate from 0.5 to 1, 2 or 3 Hz sometimes caused a large and sustained facilitation of ICa, which developed over tens of seconds, declined slowly with continued stimulation and was maintained after returning to 0.5 Hz. It is concluded that the levels of intracellular cAMP and Ca2+ mediate the initial sensitivity of ICa to changes in stimulation rate, to the extent that they determine whether or not transient facilitation will occur. Because the reduction of ICa was relatively constant, facilitation dictates the level of steady\u2010state ICa that will be reached at the higher rate. Taken together with the fact that facilitation can be modulated, the results argue for separate mechanisms of facilitation and reduction for ICa. It is suggested that the mechanism of facilitation is partly enzymatic, insofar as sustained facilitation could be a manifestation of a stimulatory Ca(2+)\u2010dependent process, which is normally counteracted by the action of phosphodiesterases.(ABSTRACT TRUNCATED AT 400 WORDS)<\/jats:p>","DOI":"10.1113\/expphysiol.1995.sp003855","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T12:46:06Z","timestamp":1418733966000},"page":"391-409","source":"Crossref","is-referenced-by-count":3,"title":["Activity\u2010induced facilitation of L\u2010type Ca2+ current in cardiomyocytes isolated from guinea\u2010pig ventricles"],"prefix":"10.1113","volume":"80","author":[{"given":"SP","family":"Kaspar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DJ","family":"Pelzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1995,5]]},"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fexpphysiol.1995.sp003855","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/expphysiol.1995.sp003855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T22:38:19Z","timestamp":1698273499000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/expphysiol.1995.sp003855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,5]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1995,5]]}},"alternative-id":["10.1113\/expphysiol.1995.sp003855"],"URL":"https:\/\/doi.org\/10.1113\/expphysiol.1995.sp003855","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,5]]}}}