Upregulated TRP and enhanced capacitative Ca(2+) entry in human pulmonary artery myocytes during proliferation.
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.
Golovina
V A
VA
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Platoshyn
O
O
Bailey
C L
CL
Wang
J
J
Limsuwan
A
A
Sweeney
M
M
Rubin
L J
LJ
Yuan
J X
JX
D001798:Blood Proteins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D050052:TRPC Cation Channels; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D001798:Blood Proteins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007093:Imidazoles; D007211:Indoles; D012333:RNA, Messenger; D050052:TRPC Cation Channels; D014665:Vasodilator Agents; C096351:transient receptor potential cation channel, subfamily C, member 1; D009532:Nickel; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid