Cell proliferation is associated with enhanced capacitative Ca(2+) entry in human arterial myocytes.
Depletion of Ca(2+) stores in the sarcoplasmic reticulum (SR) activates extracellular Ca(2+) influx via capacitative Ca(2+) entry (CCE). Here, CCE levels in proliferating and growth-arrested human pulmonary artery smooth muscle cells (PASMCs) were compared by digital imaging fluorescence microscopy. Resting cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) in proliferating PASMCs was twofold higher than that in growth-arrested cells. Cyclopiazonic acid (CPA; 10 microM), which inhibits SR Ca(2+)-ATPase and depletes inositol 1,4,5-trisphosphate-sensitive Ca(2+) stores, transiently increased [Ca(2+)](cyt) in the absence of extracellular Ca(2+). The addition of 1.8 mM Ca(2+) to the extracellular solution in the presence of CPA induced large increases in [Ca(2+)](cyt), indicative of CCE. The CPA-induced SR Ca(2+) release in proliferating PASMCs was twofold higher than that in growth-arrested cells, whereas the transient rise of [Ca(2+)](cyt) due to CCE was fivefold greater in proliferating cells. CCE was insensitive to nifedipine but was significantly inhibited by 50 mM K(+), which reduces the driving force for Ca(2+) influx, and by 0.5 mM Ni(2+), a putative blocker of store-operated Ca(2+) channels. These data show that augmented CCE is associated with proliferation of human PASMCs and may be involved in stimulating and maintaining cell growth.
Golovina
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VA
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. vgolvin@umaryland.edu
D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D008345:Manganese; D009532:Nickel; D011188:Potassium; D002118:Calcium; D016257:Fura-2; C000543:cyclopiazonic acid