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 humanTRP1 (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 viahTRP1-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.

  • This work was supported by National Heart, Lung, and Blood Institute Grants HL-54043 and HL-64945 (to J. X.-J. Yuan) and by the American Heart Association, Mid-Atlantic Affiliate (to V. Golovina). J. X.-J. Yuan is an Established Investigator of the American Heart Association.

  • Present address of J. Wang: Div. of Gastroenterology, St. Joseph's Health Center, London, Ontario N6A 4V2, Canada.

  • Address for reprint requests and other correspondence: J. X.-J. Yuan, Dept. of Medicine, Univ. of California at San Diego, 200 West Arbor Dr., San Diego, California 92103-8382 (E-mail:xiyuan{at}ucsd.edu).

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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