The phospholemman-induced modulation of Na/K ATPase Na affinity is dependent on intracellular calcium

In previous study, we found that there was store operated Ca channel (SOCC) activity in intact mouse sino-atrial node preparation, which was activated by cyclopiazonic acid (CPA), a selective sarcoplasmic reticulum (SR) Ca -ATPase inhibitor and blocked by SKF-96365, a SOCC channel inhibitor. To explore the potential implications of SOCC activity for pacemaker function, we examined the effect of CPA on spontaneous pacemaker action potentials and intracellular Ca in intact mouse SAN preparations. We found that, in the presence of CPA, there was small decrease in firing rate to 86±4% of control (n=7, P<0.005). CPA reduced the amplitude of Ca transients 48±4.5% of control (n=7, P<0.0003) and increased resting [Ca]i to 167±37% of control (P<0.0006). SKF-96365 (10 μmol/L — the same concentration that blocked SOCC) slowed firing rate to 64± 6.8% of control (P<0.01, n=4). Furthermore, SKF-96365 was able to further slow pacemaker firing to 27±4% of control when the SR Ca store was depleted by CPA. The results support the idea that CPA activates SOCC which influence Ca homeostasis and spontaneous activity in sinoatrial node.