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Am J Physiol Heart Circ Physiol 280: H746-H755, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 2, H746-H755, February 2001

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

Vera A. Golovina1,*, Oleksandr Platoshyn2,*, Colleen L. Bailey2, Jian Wang1, Alisa Limsuwan2, Michele Sweeney2, Lewis J. Rubin2, and Jason X.-J. Yuan2

1 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201; and 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, California 92103

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.

transient receptor potential gene; pulmonary hypertension; pulmonary artery smooth muscle cells

* Authors contributed equally to this work.




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J. Wang, L. A. Shimoda, and J. T. Sylvester
Capacitative calcium entry and TRPC channel proteins are expressed in rat distal pulmonary arterial smooth muscle
Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L848 - L858.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
I. Fantozzi, S. Zhang, O. Platoshyn, C. V. Remillard, R. T. Cowling, and J. X.-J. Yuan
Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells
Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1233 - L1245.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. Wang, L. G. Laurier, S. M. Sims, and H. G. Preiksaitis
Enhanced capacitative calcium entry and TRPC channel gene expression in human LES smooth muscle
Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G1074 - G1083.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
L. Lipskaia, M.-L. Pourci, C. Delomenie, L. Combettes, D. Goudouneche, J.-L. Paul, T. Capiod, and A.-M. Lompre
Phosphatidylinositol 3-Kinase and Calcium-Activated Transcription Pathways Are Required for VLDL-Induced Smooth Muscle Cell Proliferation
Circ. Res., May 30, 2003; 92(10): 1115 - 1122.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
R. M. Tribe, P. Moriarty, A. Dalrymple, A. A. Hassoni, and L. Poston
Interleukin-1{beta} Induces Calcium Transients and Enhances Basal and Store Operated Calcium Entry in Human Myometrial Smooth Muscle
Biol Reprod, May 1, 2003; 68(5): 1842 - 1849.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. M. Lee, B. J. Kim, H. J. Kim, D. K. Yang, M. H. Zhu, K. P. Lee, I. So, and K. W. Kim
TRPC5 as a candidate for the nonselective cation channel activated by muscarinic stimulation in murine stomach
Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G604 - G616.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
Y. Yu, M. Sweeney, S. Zhang, O. Platoshyn, J. Landsberg, A. Rothman, and J. X.-J. Yuan
PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression
Am J Physiol Cell Physiol, February 1, 2003; 284(2): C316 - C330.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
G.-L. Wang, X.-R. Wang, M.-J. Lin, H. He, X.-J. Lan, and Y.-Y. Guan
Deficiency in ClC-3 Chloride Channels Prevents Rat Aortic Smooth Muscle Cell Proliferation
Circ. Res., November 15, 2002; 91 (10): e28 - e32.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
R. Ma, P. E. Kudlacek, and S. C. Sansom
Protein kinase Calpha participates in activation of store-operated Ca2+ channels in human glomerular mesangial cells
Am J Physiol Cell Physiol, November 1, 2002; 283(5): C1390 - C1398.
[Abstract] [Full Text] [PDF]

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 Mol Hum ReprodHome page
A. Dalrymple, D.M. Slater, D. Beech, L. Poston, and R.M. Tribe
Molecular identification and localization of Trp homologues, putative calcium channels, in pregnant human uterus
Mol. Hum. Reprod., October 1, 2002; 8(10): 946 - 951.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
A P Albert and W A Large
Activation of store-operated channels by noradrenaline via protein kinase C in rabbit portal vein myocytes
J. Physiol., October 1, 2002; 544(1): 113 - 125.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Sweeney, Y. Yu, O. Platoshyn, S. Zhang, S. S. McDaniel, and J. X.-J. Yuan
Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation
Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L144 - L155.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
M. Sweeney, S. S. McDaniel, O. Platoshyn, S. Zhang, Y. Yu, B. R. Lapp, Y. Zhao, P. A. Thistlethwaite, and J. X.-J. Yuan
Role of capacitative Ca2+ entry in bronchial contraction and remodeling
J Appl Physiol, April 1, 2002; 92(4): 1594 - 1602.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
S. S. McDaniel, O. Platoshyn, Y. Yu, M. Sweeney, V. A. Miriel, V. A. Golovina, S. Krick, B. R. Lapp, J.-Y. Wang, and J. X.-J. Yuan
Anorexic effect of K+ channel blockade in mesenteric arterial smooth muscle and intestinal epithelial cells
J Appl Physiol, November 1, 2001; 91(5): 2322 - 2333.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. S. McDaniel, O. Platoshyn, J. Wang, Y. Yu, M. Sweeney, S. Krick, L. J. Rubin, and J. X.-J. Yuan
Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction
Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L870 - L880.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
S. Jung, R. Strotmann, G. Schultz, and T. D. Plant
TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells
Am J Physiol Cell Physiol, February 1, 2002; 282(2): C347 - C359.
[Abstract] [Full Text] [PDF]


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