Reduced store-operated Ca entry in pulmonary endothelial cells from chronically hypoxic rats

Paffett ML, Naik JS, Resta TC, Walker BR. Reduced storeoperated Ca entry in pulmonary endothelial cells from chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 293: L1135–L1142, 2007. First published August 10, 2007; doi:10.1152/ajplung.00432.2006.— Chronic hypoxia (CH)-induced pulmonary hypertension may influence basal endothelial cell (EC) intracellular Ca concentration ([Ca ]i). We hypothesized that CH decreases EC [Ca ]i associated with membrane depolarization and reduced Ca entry. To test this hypothesis, we assessed 1) basal endothelial Ca in pressurized pulmonary arteries and freshly isolated ECs, 2) EC membrane potential (Em), 3) store-operated Ca current (ISOC), and 4) store-operated Ca (SOC) entry in arteries from control and CH rats. We found that basal EC Ca was significantly lower in pressurized pulmonary arteries and freshly isolated ECs from CH rats compared with controls. Similarly, ECs in intact arteries from CH rats were depolarized compared with controls, although no differences were observed between groups in isolated cells. ISOC activation by 1 M thapsigargin displayed diminished inward current and a reversal potential closer to 0 mV in cells from CH rats compared with controls. In addition, SOC entry determined by fura 2 fluorescence and Mn quenching revealed a parallel reduction in Ca entry following CH. We conclude that differences in the magnitude of SOC entry exist between freshly dispersed ECs from CH and control rats and correlates with the decrease in basal EC [Ca ]i. In contrast, basal EC Ca influx is unaffected and membrane depolarization is limited to intact arteries, suggesting that Em may not play a major role in determining basal EC [Ca ]i following CH.