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• W2570336717 abstract "Background and Purpose The ultra‐rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5 ) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Experimental Approach Whole‐cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Key Results Human atrial I Kur was decreased by genistein (a broad‐spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration‐dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. Conclusion and Implications The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur ." @default.
• W2570336717 created "2017-01-13" @default.
• W2570336717 creator A5007309344 @default.
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• W2570336717 date "2017-02-09" @default.
• W2570336717 modified "2023-10-05" @default.
• W2570336717 title "Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K⁺current of human atria by inhibiting EGF receptor tyrosine kinase" @default.
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• W2570336717 doi "https://doi.org/10.1111/bph.13710" @default.
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