Upregulated<i>TRP</i>and enhanced capacitative Ca²⁺entry in human pulmonary artery myocytes during proliferation

<jats:p>A rise in cytosolic Ca<jats:sup>2+</jats:sup>concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>cyt</jats:sub>) due to Ca<jats:sup>2+</jats:sup>release from intracellular Ca<jats:sup>2+</jats:sup>stores and Ca<jats:sup>2+</jats:sup>influx through plasmalemmal Ca<jats:sup>2+</jats:sup>channels plays a critical role in mitogen-mediated cell growth. Depletion of intracellular Ca<jats:sup>2+</jats:sup>stores triggers capacitative Ca<jats:sup>2+</jats:sup>entry (CCE), a mechanism involved in maintaining Ca<jats:sup>2+</jats:sup>influx and refilling intracellular Ca<jats:sup>2+</jats:sup>stores. Transient receptor potential ( TRP) genes have been demonstrated to encode the store-operated Ca<jats:sup>2+</jats:sup>channels that are activated by Ca<jats:sup>2+</jats:sup>store depletion. In this study, we examined whether CCE, activity of store-operated Ca<jats:sup>2+</jats:sup>channels, and human TRP1 ( hTRP1) expression are essential in human pulmonary arterial smooth muscle cell (PASMC) proliferation. Chelation of extracellular Ca<jats:sup>2+</jats:sup>and depletion of intracellularly stored Ca<jats:sup>2+</jats:sup>inhibited PASMC growth in media containing serum and growth factors. Resting [Ca<jats:sup>2+</jats:sup>]<jats:sub>cyt</jats:sub>as well as the increases in [Ca<jats:sup>2+</jats:sup>]<jats:sub>cyt</jats:sub>due to Ca<jats:sup>2+</jats:sup>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 Ca<jats:sup>2+</jats:sup>stores and the mRNA level of hTRP1 were much greater in proliferating PASMC than in growth-arrested cells. These results suggest that elevated [Ca<jats:sup>2+</jats:sup>]<jats:sub>cyt</jats:sub>and intracellularly stored [Ca<jats:sup>2+</jats:sup>] play an important role in pulmonary vascular smooth muscle cell growth. CCE, potentially via hTRP1-encoded Ca<jats:sup>2+</jats:sup>-permeable channels, may be an important mechanism required to maintain the elevated [Ca<jats:sup>2+</jats:sup>]<jats:sub>cyt</jats:sub>and stored [Ca<jats:sup>2+</jats:sup>] in human PASMC during proliferation.</jats:p>