RESUMEN
In Ca(2+)-overloaded ventricular myocytes, SERCA is crucial to steadily achieve the critical sarcoplasmic reticulum (SR) Ca(2+) level to trigger and sustain Ca(2+) waves, that propagate at constant rate (Êwave). High luminal Ca(2+) sensitizes RyR2, thereby increasing Ca(2+) sparks frequency, and the larger RyR2-mediated SR Ca(2+) flux (dF/dt) sequentially activates adjacent RyR2 clusters. Recently, it was proposed that rapid SERCA Ca(2+) reuptake, ahead of the wave front, further sensitizes RyR2, increasing Êwave. Nevertheless, this is controversial because rapid cytosolic Ca(2+) removal could instead impair RyR2 activation. We assessed whether rapid SR Ca(2+) uptake enhances Êwave by changing SERCA activity (Ò¡Decay) over a large range (â¼175%). We used normal (Ctrl) and hyperthyroid rat (HT; reduced phospholamban by â¼80%) myocytes treated with thapsigargin or isoproterenol (ISO). We found that Êwave and dF/dt had a non-linear dependency with Ò¡Decay, while Ca(2+) waves amplitude was largely unaffected. Furthermore, SR Ca(2+) also showed a non-linear dependency with Ò¡Decay, however, the relationships Êwave vs. SR Ca(2+) and Êwave vs. dF/dt were linear, suggesting that high steady state SR Ca(2+) determines Êwave, while rapid SERCA Ca(2+) uptake does not. Finally, ISO did not increase Êwave in HT cells, therefore, ISO-enhanced Êwave in Ctrl depended on high SR Ca(2+).