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 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 Kvβ₂ and accelerated I_K(V) inactivation. Furthermore. E_m 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 I_K(V). The resultant membrane depolarization increases [Ca²⁺]_cyt and enhances PASMC growth.