Abstract: | Depletion of Ca2+ stores inthe sarcoplasmic reticulum (SR) activates extracellularCa2+ influx via capacitativeCa2+ entry (CCE). Here, CCE levelsin proliferating and growth-arrested human pulmonary artery smoothmuscle cells (PASMCs) were compared by digital imaging fluorescencemicroscopy. Resting cytosolic freeCa2+ concentration(Ca2+]cyt)in proliferating PASMCs was twofold higher than that in growth-arrestedcells. Cyclopiazonic acid (CPA; 10 µM), which inhibits SRCa2+-ATPase and depletes inositol1,4,5-trisphosphate-sensitiveCa2+ stores, transiently increasedCa2+]cytin the absence of extracellularCa2+. The addition of 1.8 mMCa2+ to the extracellular solutionin the presence of CPA induced large increases inCa2+]cyt,indicative of CCE. The CPA-induced SRCa2+ release in proliferatingPASMCs was twofold higher than that in growth-arrested cells, whereasthe transient rise ofCa2+]cytdue to CCE was fivefold greater in proliferating cells. CCE wasinsensitive to nifedipine but was significantly inhibited by 50 mMK+, which reduces the drivingforce for Ca2+ influx, and by 0.5 mM Ni2+, a putative blocker ofstore-operated Ca2+ channels.These data show that augmented CCE is associated with proliferation ofhuman PASMCs and may be involved in stimulating and maintaining cell growth. |