Sarcoplasmic Reticulum Ca Pumping Kinetics Regulates Timing of Local Ca Releases and Spontaneous Beating Rate of Rabbit Sinoatrial Node Pacemaker Cells

Rationale: Sinoatrial node cells (SANCs) generate local, subsarcolemmal Ca releases (LCRs) from sarcoplasmic reticulum (SR) during late diastolic depolarization. LCRs activate an inward Na -Ca exchange current (INCX), which accelerates diastolic depolarization rate, prompting the next action potential (AP). The LCR period, ie, a delay between AP-induced Ca transient and LCR appearance, defines the time of late diastolic depolarization INCX activation. Mechanisms that control the LCR period, however, are still unidentified. Objective: To determine dependence of the LCR period on SR Ca refilling kinetics and establish links between regulation of SR Ca replenishment, LCR period, and spontaneous cycle length. Methods and Results: Spontaneous APs and SR luminal or cytosolic Ca were recorded using perforated patch and confocal microscopy, respectively. Time to 90% replenishment of SR Ca following AP-induced Ca transient was highly correlated with the time to 90% decay of cytosolic Ca transient (T-90C). Local SR Ca 2