Background-Activity of voltage-gated K+ (K-v) channels controls membrane po
tential (E-m) that regulates cytosolic free Ca2+ concentration ([Ca2+](cyt)
) by regulating voltage-dependent Ca2+ channel function. A rise in [Ca2+](c
yt) in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstrict
ion and stimulates PASMC proliferation. Whether c-Jun, a transcription fact
or that stimulates cell proliferation, affects Kv channel activity in PASMC
s 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 ad
enovirus). Using single-cell reverse transcription-polymerase chain reactio
n, 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 cell
s and cells infected with antisense c-jun. Overexpression of c-Jun also upr
egulated protein expression of Kv beta (2) and accelerated I-K(V) inactivat
ion. 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 i
s associated with a decrease in I-K(V). The resultant membrane depolarizati
on increases [Ca2+](cyt) and enhances PASMC growth.