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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.

biomed research international

Effect of Ca2+Efflux Pathway Distribution and Exogenous Ca2+Buffers on Intracellular Ca2+Dynamics in the Rat Ventricular Myocyte: A Simulation Study