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

Vera A. Golovina, Oleksandr Platoshyn, Colleen L. Bailey, Jian Wang, Alisa Limsuwan, Michele Sweeney, Lewis J. Rubin, Jason X.J. Yuan

Research output: Contribution to journalArticlepeer-review

305 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)H746-H755
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
DOIs
StatePublished - Feb 2001

Keywords

  • Pulmonary artery smooth muscle cells
  • Pulmonary hypertension
  • Transient receptor potential gene

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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