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

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 Kvβ...