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(Circulation. 2001;104:1557.)
© 2001 American Heart Association, Inc.

Basic Science Reports

c-Jun Decreases Voltage-Gated K⁺ Channel Activity in Pulmonary Artery Smooth Muscle Cells

Ying Yu, MD, PhD^*; Oleksandr Platoshyn, MS^*; Jifeng Zhang, PhD^*; Stefanie Krick, MD; Ying Zhao, BS; Lewis J. Rubin, MD; Abraham Rothman, MD; Jason X.-J. Yuan, MD, PhD

From the Departments of Medicine (Y.Y., O.P., S.K., Y.Z., L.J.R., J.X.-J.Y.) and Pediatrics (J.Z., A.R.), University of California, San Diego.

Correspondence to Jason X.-J. Yuan, MD, PhD, Division of Pulmonary and Critical Care Medicine, University of California, San Diego, 200 W Arbor Dr, San Diego, CA 92103-8382. E-mail xiyuan{at}ucsd.edu

Background— Activity of voltage-gated K⁺ (K_v) channels controls membrane potential (E_m) that regulates cytosolic free Ca²⁺ concentration ([Ca²⁺]_cyt) by regulating voltage-dependent Ca²⁺ channel function. A rise in [Ca²⁺]_cyt in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a transcription factor that stimulates cell proliferation, affects K_v channel activity in PASMCs was investigated.

Methods and Results— Infection of primary cultured PASMCs with an adenoviral vector expressing c-jun increased the protein level of c-Jun and reduced K_v currents (I_K(V)) compared with control cells (infected with an empty adenovirus). Using single-cell reverse transcription–polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the current density of I_K(V) were both attenuated in c-jun–infected PASMCs compared with control cells and cells infected with antisense c-jun. Overexpression of c-Jun also upregulated protein expression of Kvß₂ and accelerated I_K(V) inactivation. Furthermore, E_m was more depolarized and [³H]thymidine incorporation was greater in PASMCs infected with c-jun than in control cells and cells infected with antisense c-jun.

Conclusions— These results suggest that c-Jun–mediated PASMC proliferation is associated with a decrease in I_K(V). The resultant membrane depolarization increases [Ca²⁺]_cyt and enhances PASMC growth.

Key Words: transcription factors • ion channels • genes • lung • remodeling

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