The role of sarcolemmal Ca2+-ATPase in the regulation of resting calcium concentration in rat ventricular myocytes.

1. The aim of this work was to investigate the role of sarcolemmal Ca2+-ATPase in rat ventricular myocytes. We have measured intracellular Ca2+ concentration ([Ca2+]i) using indo-1. The actions of the ATPase inhibitor carboxyeosin were studied. 2. Carboxyeosin increased resting [Ca2+]i and the magnitude of the systolic Ca2+ transient and slowed the rate of its relaxation by 5 %. 3. Carboxyeosin increased the magnitude of the caffeine-evoked increase in [Ca2+]i and slowed its relaxation by 20 %. Removal of extracellular Na+ slowed the rate constant by 80 %. When Na+ was removed in a carboxyeosin-treated cell, the caffeine-evoked increase in [Ca2+]i did not decay. 4. Carboxyeosin increased the integral of the Na+-Ca2+ exchange current activated by caffeine. This is, in part, due to an increase in sarcoplasmic reticulum Ca2+ content. 5. When extracellular Na+ was removed, there was a transient increase in [Ca2+]i which then decayed. The rate of this decay was slowed by carboxyeosin by a factor of about four. The residual decay could be abolished with caffeine. 6. In the absence of extracellular Na+, increasing extracellular Ca2+ concentration ([Ca2+]o) elevated [Ca2+]i. In carboxyeosin-treated cells, [Ca2+]i was much more sensitive to [Ca2+]o. 7. These results demonstrate the role of a carboxyeosin-sensitive Ca2+-ATPase in the control of resting [Ca2+]i and the reduction in [Ca2+]i following an increase in [Ca2+]i.