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(Circulation Research. 2005;96:864.)
© 2005 American Heart Association, Inc.

Cellular Biology

Low-Voltage-Activated (T-Type) Calcium Channels Control Proliferation of Human Pulmonary Artery Myocytes

David M. Rodman, Katherine Reese, Julie Harral, Brian Fouty, Songwei Wu, James West, Marloes Hoedt-Miller, Yuji Tada, Kai-Xun Li, Carlyne Cool, Karen Fagan, Leanne Cribbs

From the Center for Genetic Lung Disease (D.M.R., K.R., J.H., B.F., J.W, M.H.-M., Y.T., K.-X.L., K.F.), Division of Pulmonary Sciences and Critical Care Medicine, and Department of Pathology (S.W.), University of Colorado Health Sciences Center, Denver, Colo; University of South Alabama (C.C.), Mobile, Ala; and Loyola University (L.C.), Chicago, Ill.

Correspondence to Dr David Rodman, CVP Research Laboratory, University of Colorado Health Sciences Center, B-133, 4200 9th Ave, Denver, CO 80262. E-mail david.rodman{at}uchsc.edu

While Ca²⁺ influx is essential for activation of the cell cycle machinery, the processes that regulate Ca²⁺ influx in this context have not been fully elucidated. Electrophysiological and molecular studies have identified multiple Ca²⁺ channel genes expressed in mammalian cells. Ca_v3.x gene family members, encoding low voltage-activated (LVA) or T-type channels, were first identified in the central nervous system and subsequently in non-neuronal tissue. Reports of a potential role for T-type Ca²⁺ channels in controlling cell proliferation conflict. The present study tested the hypothesis that T-type Ca²⁺ channels, encoded by Ca_v3.x genes, control pulmonary artery smooth muscle cell proliferation and cell cycle progression. Using quantitative RT/PCR, immunocytochemistry, and immunohistochemistry we found that Ca_v3.1 was the predominant Ca_v3.x channel expressed in early passage human pulmonary artery smooth muscle cells in vitro and in the media of human pulmonary arteries, in vivo. Selective blockade of Ca_v3.1 expression with small interfering RNA (siRNA) and pharmacological blockade of T-type channels completely inhibited proliferation in response to 5% serum and prevented cell cycle entry. These studies establish that T-type voltage-operated Ca²⁺ channels are required for cell cycle progression and proliferation of human PA SMC.

Key Words: T-type calcium channel • pulmonary artery • smooth muscle cells • proliferation

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