c-Jun decreases voltage-gated K(+) channel activity in pulmonary artery smooth muscle cells.
Circulation
; 104(13): 1557-63, 2001 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-11571252
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 ANDRESULTS:
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 Kvbeta(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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Proteínas Proto-Oncogênicas c-jun
/
Músculo Liso
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2001
Tipo de documento:
Article