title: Effect of Ca2+ efflux pathway distribution and exogenous Ca2+ buffers on intracellular Ca2+ dynamics in the rat ventricular myocyte: a simulation study.
abstract: We have used a previously published computer model of the rat cardiac ventricular myocyte to investigate the effect of changing the distribution of Ca(2+) efflux pathways (SERCA, Na(+)/Ca(2+) exchange, and sarcolemmal Ca(2+) ATPase) between the dyad and bulk cytoplasm and the effect of adding exogenous Ca(2+) buffers (BAPTA or EGTA), which are used experimentally to differentially buffer Ca(2+) in the dyad and bulk cytoplasm, on cellular Ca(2+) cycling. Increasing the dyadic fraction of a particular Ca(2+) efflux pathway increases the amount of Ca(2+) removed by that pathway, with corresponding changes in Ca(2+) efflux from the bulk cytoplasm. The magnitude of these effects varies with the proportion of the total Ca(2+) removed from the cytoplasm by that pathway. Differences in the response to EGTA and BAPTA, including changes in Ca(2+)-dependent inactivation of the L-type Ca(2+) current, resulted from the buffers acting as slow and fast "shuttles," respectively, removing Ca(2+) from the dyadic space. The data suggest that complex changes in dyadic Ca(2+) and cellular Ca(2+) cycling occur as a result of changes in the location of Ca(2+) removal pathways or the presence of exogenous Ca(2+) buffers, although changing the distribution of Ca(2+) efflux pathways has relatively small effects on the systolic Ca(2+) transient.
authors: Institute of Thermomechanics, Branch Brno, Academy of Science of the Czech Republic, Technická 2, 61669 Brno, Czech Republic ; Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
authors: Michal
authors: 0000-0001-8198-1215
authors: M
authors: Pásek
authors: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
authors: Jiří
authors: J
authors: Simurda
authors: School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors: Clive H
authors: CH
authors: Orchard
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D003198:Computer Simulation; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors
chemical_list: D002021:Buffers; D019831:Sodium-Calcium Exchanger; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium