c-Jun decreases voltage-gated K+ channel activity in pulmonary artery smooth muscle cells

Y. Yu, O. Platoshyn, J. Zhang, S. Krick, Y. Zhao, L. J. Rubin, A. Rothman, J. X.J. Yuan

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Abstract

Background - Activity of voltage-gated K+ (Kv) channels controls membrane potential (Em) 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 Kv 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 Kv currents (IK(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 IK(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 Kvβ2 and accelerated IK(V) inactivation. Furthermore. Em 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 IK(V). The resultant membrane depolarization increases [Ca2+]cyt and enhances PASMC growth.

Original languageEnglish (US)
Pages (from-to)1557-1563
Number of pages7
JournalCirculation
Volume104
Issue number13
DOIs
StatePublished - Sep 25 2001
Externally publishedYes

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Keywords

  • Genes
  • Ion channels
  • Lung
  • Remodeling
  • Transcription factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Yu, Y., Platoshyn, O., Zhang, J., Krick, S., Zhao, Y., Rubin, L. J., Rothman, A., & Yuan, J. X. J. (2001). c-Jun decreases voltage-gated K+ channel activity in pulmonary artery smooth muscle cells. Circulation, 104(13), 1557-1563. https://doi.org/10.1161/hc3801.095662