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

Academic Article

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 KvĪ²2 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.
  • Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yu Y; Platoshyn O; Zhang J; Krick S; Zhao Y; Rubin LJ; Rothman A; Yuan JXJ
  • Start Page

  • 1557
  • End Page

  • 1563
  • Volume

  • 104
  • Issue

  • 13