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Am J Physiol Heart Circ Physiol 280: H746-H755, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 2, H746-H755, February 2001

Upregulated TRP and enhanced capacitative Ca2+ entry in human pulmonary artery myocytes during proliferation

Vera A. Golovina1,*, Oleksandr Platoshyn2,*, Colleen L. Bailey2, Jian Wang1, Alisa Limsuwan2, Michele Sweeney2, Lewis J. Rubin2, and Jason X.-J. Yuan2

1 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201; and 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, California 92103

A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) due to Ca2+ release from intracellular Ca2+ stores and Ca2+ influx through plasmalemmal Ca2+ channels plays a critical role in mitogen-mediated cell growth. Depletion of intracellular Ca2+ stores triggers capacitative Ca2+ entry (CCE), a mechanism involved in maintaining Ca2+ influx and refilling intracellular Ca2+ stores. Transient receptor potential (TRP) genes have been demonstrated to encode the store-operated Ca2+ channels that are activated by Ca2+ store depletion. In this study, we examined whether CCE, activity of store-operated Ca2+ channels, and human TRP1 (hTRP1) expression are essential in human pulmonary arterial smooth muscle cell (PASMC) proliferation. Chelation of extracellular Ca2+ and depletion of intracellularly stored Ca2+ inhibited PASMC growth in media containing serum and growth factors. Resting [Ca2+]cyt as well as the increases in [Ca2+]cyt due to Ca2+ release and CCE were all significantly greater in proliferating PASMC than in growth-arrested cells. Consistently, whole cell inward currents activated by depletion of intracellular Ca2+ stores and the mRNA level of hTRP1 were much greater in proliferating PASMC than in growth-arrested cells. These results suggest that elevated [Ca2+]cyt and intracellularly stored [Ca2+] play an important role in pulmonary vascular smooth muscle cell growth. CCE, potentially via hTRP1-encoded Ca2+-permeable channels, may be an important mechanism required to maintain the elevated [Ca2+]cyt and stored [Ca2+] in human PASMC during proliferation.

transient receptor potential gene; pulmonary hypertension; pulmonary artery smooth muscle cells

* Authors contributed equally to this work.




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