Sarcoplasmic Reticulum Ca2+ Pumping Kinetics Regulates Timing of Local Ca2+ Releases and Spontaneous Beating Rate of Rabbit Sinoatrial Node Pacemaker Cells

Rationale: Sinoatrial node cells (SANCs) generate local, subsarcolemmal Ca2+ releases (LCRs) from sarcoplasmic reticulum (SR) during late diastolic depolarization. LCRs activate an inward Na+-Ca2+ exchange current (I-NCX), which accelerates diastolic depolarization rate, prompting the next action potential (AP). The LCR period, ie, a delay between AP-induced Ca2+ transient and LCR appearance, defines the time of late diastolic depolarization I-NCX activation. Mechanisms that control the LCR period, however, are still unidentified. Objective: To determine dependence of the LCR period on SR Ca2+ refilling kinetics and establish links between regulation of SR Ca2+ replenishment, LCR period, and spontaneous cycle length. Methods and Results: Spontaneous APs and SR luminal or cytosolic Ca2+ were recorded using perforated patch and confocal microscopy, respectively. Time to 90% replenishment of SR Ca2+ following AP-induced Ca2+ transient was highly correlate