Susceptibility of cloned K+ channels to reactive oxygen species.
Free radical-induced oxidant stress has been implicated in a number of physiological and pathophysiological states including ischemia and reperfusion-induced dysrhythmia in the heart, apoptosis of T lymphocytes, phagocytosis, and neurodegeneration. We have studied the effects of oxidant stress on the native K+ channel from T lymphocytes and on K+ channels cloned from cardiac, brain, and T-lymphocyte cells and expressed in Xenopus oocytes. The activity of three Shaker K+ channels (Kv1.3, Kv1.4, and Kv1.5), one Shaw channel (Kv3.4), and one inward rectifier K+ channel (IRK3) was drastically inhibited by photoactivation of rose bengal, a classical generator of reactive oxygen species. Other channel types (such as Shaker K+ channel Kv1.2, Shab channels Kv2.1 and Kv2.2, Shal channel Kv4.1, inward rectifiers IRK1 and ROMK1, and hIsK) were completely resistant to this treatment. On the other hand tert-butyl hydroperoxide, another generator of reactive oxygen species, removed the fast inactivation processes of Kv1.4 and Kv3.4 but did not alter other channels. Xanthine/xanthine oxidase system had no effect on all channels studied. Thus, we show that different types of K+ channels are differently modified by reactive oxygen species, an observation that might be of importance in disease states.
Duprat
F
F
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Guillemare
E
E
Romey
G
G
Fink
M
M
Lesage
F
F
Lazdunski
M
M
Honore
E
E
D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D008027:Light; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010545:Peroxides; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D017382:Reactive Oxygen Species / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000378:metabolism; D012395:Rose Bengal / Q000528:radiation effects; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; D019820:Xanthine; D014969:Xanthine Oxidase; D014970:Xanthines; D014981:Xenopus; D020122:tert-Butylhydroperoxide
D051668:Delayed Rectifier Potassium Channels; C490969:Kcnj4 protein, mouse; D010545:Peroxides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; D014970:Xanthines; D019820:Xanthine; D012395:Rose Bengal; D020122:tert-Butylhydroperoxide; D014969:Xanthine Oxidase