DIASTOLIC SR CA EFFLUX IN ATRIAL PACEMAKER CELLS AND CA-OVERLOADED MYOCYTES

Evidence has shown that the sarcoplasmic reticulum (SR) of cardiac cel ls releases Ca not only during excitation-contraction coupling but als o during diastole, albeit at a much lower rate. This diastolic SR Ca r elease (leak) has also been implicated in the generation of spontaneou s depolarization in latent atrial pacemaker cells of the cat right atr ium. In the present work, we sought to measure Ca transients in pacema ker and nonpacemaker cells of the cat using the fluorescent Ca indicat or indo 1. Atrial latent pacemaker cells develop a slow Ca transient w hen rested in the presence of both Na- and Ca-free solution and thapsi gargin [used to inhibit Na/Ca exchange and SR Ca adenosinetriphosphata se (Ca-ATPase), respectively]. This increase in cytosolic Ca concentra tion ([Ca](i)) is probably caused by the rate of SR Ca leak exceeding the capacity of the remaining Ca transport systems (e.g., sarcolemmal Ca-ATPase and mitochondrial Ca uptake). However, neither cat sinoatria l (SA) node cells nor myocytes from cat atrium or ventricle exhibited a similar increase in [Ca](i) during the same protocol. This indicates that SR Ca leak in these cells occurred at a rate low enough to be wi thin the capacity of the slow Ca transporters, as observed previously in rabbit ventricular myocytes. When atrial and ventricular myocytes w ere stimulated at higher frequencies, sufficient to markedly increase diastolic and systolic [Ca](i) and approach Ca overload (and spontaneo us activity), they responded to inhibition of SR Ca-ATPase and Na/Ca e xchange with a slow Ca transient similar to that normally observed in atrial latent pacemaker cells. Furthermore, the SR Ca depletion by tha psigargin did not affect spontaneous activity of SA node cells, but it prevented or slowed pacemaker activity in the atrial latent pacemaker cells. These findings suggest that enhanced diastolic SR Ca efflux co ntributes significantly to the generation of spontaneous activity in a trial subsidiary pacemakers under normal conditions and in Ca-overload ed myocytes but not in SA node cells.