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

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 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 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 Kv beta (2) and accelerated I-K(V) inactivation. Furthermore, E-m was more depolarized and [H-3]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 e-Jun-mediated PASMC proliferation is associated with a decrease in I-K(V). The resultant membrane depolarization increases [Ca2+](cyt) and enhances PASMC growth.