Mitogen-activated protein kinases control cardiac KChIP2 gene expression.

ABSTRACT: Hypertrophied myocardium is associated with reductions in the transient outward K(+) current (Ito) and expression of pore-forming Kv4.2/4.3 and auxiliary KChIP2 subunits. Here we show that KChIP2 mRNA and protein levels are dramatically decreased to 10% to 30% of control levels in the left ventricle of aorta-constricted rats in vivo and phenylephrine (PE)-treated myocytes in vitro. PE also markedly decreases Ito density. Inhibition of protein kinase Cs (PKCs) does not affect the PE-induced reduction in KChIP2 mRNA level, whereas activation of PKC with phorbol ester (phorbol myristate [PMA]) causes a marked reduction in KChIP2 mRNA level. Pharmacological inhibition of MEKs or overexpression of a dominant-negative MEK1 increases the basal KChIP2 mRNA expression and blocks the PMA-induced dec

SUBMITTER: Jia Y 

PROVIDER: S-EPMC1373668 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature