The cardiac acetylcholine-activated, inwardly rectifying K+-channel subunit GIRK1 gives rise to an inward current induced by free oxygen radicals.
Free Radic Biol Med
; 26(3-4): 253-9, 1999 Feb.
Article
em En
| MEDLINE
| ID: mdl-9895214
ABSTRACT
Reactive oxygen species (ROS) play a crucial role in pathophysiology of the cardiovascular system. The present study was designed to analyze the redox sensitivity of G-protein-activated inward rectifier K+ (GIRK) channels, which control cardiac contractility and excitability. GIRK1 subunits were heterologously expressed in Xenopus laevis oocytes and the resulting K+ currents were measured with the two-electrode voltage clamp technique. Oxygen free radicals generated by the hypoxanthine/xanthine oxidase system led to a marked increase in the current through GIRK channels, termed superoxide-induced current (I(SO)). Furthermore, I(SO) did not depend on G-protein-dependent activation of GIRK currents by coexpressed muscarinic m2-receptors, but could also be observed when no agonist was present in the bathing solution. Niflumic acid at a concentration of 0.5 mmol/l did not abolish I(SO), whereas 100 micromol/l Ba2+ attenuated I(SO) completely. Catalase (10(6) i.u./l) failed to suppress I(SO), whereas H2O2 concentration was kept close to zero, as measured by chemiluminescence. Hence, we conclude that O2*- or a closely related species is responsible for I(SO) induction. Our results demonstrate a significant redox sensitivity of GIRK1 channels and suggest redox-activation of G-protein-activated inward rectifier K+ channels as a key mechanism in oxidative stress-associated cardiac dysfunction.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Acetilcolina
/
Receptores Muscarínicos
/
Espécies Reativas de Oxigênio
/
Canais de Potássio Corretores do Fluxo de Internalização
/
Contração Miocárdica
Limite:
Animals
Idioma:
En
Revista:
Free Radic Biol Med
Assunto da revista:
BIOQUIMICA
/
MEDICINA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Áustria