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

Abstract

Background Activity of voltage-gated K + (K v ) channels controls membrane potential (E m ) that regulates cytosolic free Ca 2+ concentration ([Ca 2+ ] cyt ) by regulating voltage-dependent Ca 2+ channel function. A rise in [Ca 2+ ] 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 Kvβ 2 and accelerated I K(V) inactivation. Furthermore, E m was more depolarized and [ 3 H]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 [Ca 2+ ] cyt and enhances PASMC growth.