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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAFyBHm7Vid3riqSZeC0osS9tIW7CHcYcWw-Gh0-Xp5zs#_6 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAFyBHm7Vid3riqSZeC0osS9tIW7CHcYcWw-Gh0-Xp5zs#_5 http://www.w3.org/ns/prov#value Vinogradova et al. (508) have reported that basal PKA activity is higher in rabbit SAN cells than in working myocytes. High phosphorylation of PLB and RyRs generates periodical LCICR causing INCX-mediated membrane voltage oscillations, which contribute to the control of the chronotropic state of the cell (43, 508). .....Figure 23. In pacemaker cells, high basal cAMP-mediated PKA-dependent phosphorylation stimulates a perpetual \"free running\" Ca2+ cycling by pumping Ca2+ into the SR via SERCA2 and LCICR via RyRs. PKA also stimulates Ca2+ entry through Cav1.3-mediated ICa,L. The thick red line indicates the persistent spontaneous Ca2+ cycling. The possibility that Cav3.1-mediated ICa,T can contribute to replenishment of SR Ca2+ stores is suggested. Spontaneous LCICR from SR is linked to the diastolic depolarization via Ca2+ activation of inward INCX current. Direct cAMP-dependent activation of HCN channels or cAMP-mediated, PKA-dependent phosphorylation of Cav1.3 channels and Ist (dashed lines) strongly stimulates the pacemaker cycle driven by the \"membrane ion channels clock\" (MCC). It is conceivable that the MCC can entrain the intracellular Ca2+ clock because of the dependency of SR Ca2+ content from VDCCs. 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