Upregulated TRP and enhanced capacitative Ca(2+) entry in human pulmonary artery myocytes during proliferation

• Published in: American journal of physiology. Heart and circulatory physiology 2001-02, Vol.280 (2), p.H746-H755
• Main Authors: Golovina, V A, Platoshyn, O, Bailey, C L, Wang, J, Limsuwan, A, Sweeney, M, Rubin, L J, Yuan, J X
• Format: Article
• Language: English
• Subjects: Blood Proteins - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Channels, L-Type - metabolism; Cell Division - drug effects; Cell Division - physiology; Cells, Cultured; Gene Expression - physiology; Humans; Hypertension, Pulmonary - metabolism; Imidazoles - pharmacology; Indoles - pharmacology; Membrane Potentials - physiology; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Nickel - pharmacology; Nifedipine - pharmacology; Patch-Clamp Techniques; Pulmonary Artery - cytology; Pulmonary Artery - metabolism; RNA, Messenger - analysis; TRPC Cation Channels; Up-Regulation - drug effects; Up-Regulation - physiology; Vasodilator Agents - pharmacology
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.2001.280.2.h746

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