Abstract
The S631C mutation in human ether-à-go-go-related gene (HERG) channels has previously been reported to disrupt C-type inactivation and ion-selectivity when Cys-631 is in the oxidized state. In this study, we report the relation between pharmacology and C-type inactivation for HERGS631C channels. We demonstrate that HERGS631C in its reduced state is fully blocked by 1 microM astemizole, terfenadine and dofetilide, similar to wild-type HERG channels. In contrast, oxidized HERGS631C is insensitive for these blockers. Our results suggest that an interaction with HERG channels in the inactivated state might be a common mechanism to a variety of drugs known to block HERG channels with high affinity.
MeSH terms
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Animals
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Astemizole / pharmacology
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Cation Transport Proteins*
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DNA-Binding Proteins*
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ERG1 Potassium Channel
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Electric Conductivity
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Ether-A-Go-Go Potassium Channels
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Female
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Gene Expression
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Humans
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Microelectrodes
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Mutation*
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Oocytes / metabolism
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Oxidation-Reduction
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Patch-Clamp Techniques
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Phenethylamines / pharmacology
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Potassium Channels / drug effects*
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Potassium Channels / genetics*
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Potassium Channels / physiology
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Potassium Channels, Voltage-Gated*
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Sulfonamides / pharmacology
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Terfenadine / pharmacology
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Trans-Activators*
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Transcriptional Regulator ERG
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Transfection
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Xenopus
Substances
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Cation Transport Proteins
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DNA-Binding Proteins
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ERG protein, human
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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KCNH2 protein, human
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KCNH6 protein, human
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Phenethylamines
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Sulfonamides
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Trans-Activators
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Transcriptional Regulator ERG
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Terfenadine
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Astemizole
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dofetilide