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- W1465685963 abstract "The human ether-a-go-go related gene (hERG)-encoded potassium channel conducts an important current for the repolarization of cardiac action potentials. hERG channel dysfunction leads to abnormal cardiac electrical activities characterized by a prolonged QT interval. We have previously shown that exposure of hERG-expressing HEK cells to a 0 mM K+medium induces vigorous internalization of hERG but not ether-a-go-go (EAG) channels from the plasma membrane. To investigate the mechanisms of 0 mM K+-induced hERG endocytosis, we used a chimerical channel model constructed by combining hERG and EAG, as well as drugs that bind to either the internal pore mouth of the hERG channel (E-4031) or the extracellular edge of the pore entrance (BeKm-1). Using Western blot analysis and whole-cell patch clamp, our data show that replacing the S5-S6 linker of hERG with that of bovine EAG prevented 0 mM K+-induced hERG endocytosis. Moreover, BeKm-1 prevented 0 mM K+-induced hERG internalization. Under the whole-cell voltage clamp configuration, acute exposure of hERG-expressing HEK cells to 0 mM K+ solution eliminated hERG conductance within 5 minutes, and the hERG conductance recovered slowly upon re-exposure to 5 mM K+ solution. The 0 mM K+ exposure-induced conductance loss was completely prevented by the application of BeKm-1 (1 µM). We conclude that a conformational change in the outer pore-mouth of hERG occurs upon removal of extracellular K+, which triggers hERG internalization. BeKm-1 prevents such conformational change and the subsequent internalization of hERG channels under 0 mM K+ culture conditions. (Supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Ontario)" @default.
- W1465685963 created "2016-06-24" @default.
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- W1465685963 date "2015-04-01" @default.
- W1465685963 modified "2023-09-24" @default.
- W1465685963 title "Scorpion Toxin BeKm‐1 Blocks Low K + ‐induced Endocytosis of Cell‐surface Human Ether‐a‐go‐go Related Gene (hERG) Channels" @default.
- W1465685963 doi "https://doi.org/10.1096/fasebj.29.1_supplement.714.11" @default.
- W1465685963 hasPublicationYear "2015" @default.
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