Abstract
We used Xenopus oocytes co-expressing thyrotropin-releasing hormone (TRH) receptors and human ether-a-go-go-related gene (HERG) K+ channel variants carrying different amino-terminal modifications to check the relevance of the proximal domain for hormonal regulation of the channel. Deletion of the whole proximal domain (Delta 138-373) eliminates TRH-induced modifications in activation and deactivation parameters. TRH effects on activation are also suppressed with channels lacking the second half of the proximal domain or only residues 326-373. However, normal responses to TRH are obtained with Delta 346-373 channels. Thus, whereas residues 326-345 are required for the hormonal modulation of HERG activation, different proximal domain sequences contribute to set HERG gating characteristics and its regulation by TRH.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cation Transport Proteins*
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Cell Line
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DNA-Binding Proteins*
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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Humans
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology
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Kidney / cytology
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Kidney / drug effects
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Kidney / metabolism
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Mutagenesis, Site-Directed
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Oocytes / drug effects
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Oocytes / metabolism
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Patch-Clamp Techniques
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Potassium Channels / chemistry
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Potassium Channels, Voltage-Gated*
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Protein Structure, Tertiary / physiology
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Receptors, Thyrotropin-Releasing Hormone / genetics
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Receptors, Thyrotropin-Releasing Hormone / metabolism*
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Sequence Deletion
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Structure-Activity Relationship
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Thyrotropin-Releasing Hormone / pharmacology
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Trans-Activators*
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Transcriptional Regulator ERG
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Transfection
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Type C Phospholipases / metabolism*
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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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Potassium Channels
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Potassium Channels, Voltage-Gated
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Receptors, Thyrotropin-Releasing Hormone
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Trans-Activators
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Transcriptional Regulator ERG
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Thyrotropin-Releasing Hormone
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Type C Phospholipases