Relevance of the proximal domain in the amino-terminus of HERG channels for regulation by a phospholipase C-coupled hormone receptor

FEBS Lett. 2003 Jan 30;535(1-3):125-30. doi: 10.1016/s0014-5793(02)03888-7.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins*
  • Cell Line
  • DNA-Binding Proteins*
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism
  • Mutagenesis, Site-Directed
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Structure, Tertiary / physiology
  • Receptors, Thyrotropin-Releasing Hormone / genetics
  • Receptors, Thyrotropin-Releasing Hormone / metabolism*
  • Sequence Deletion
  • Structure-Activity Relationship
  • Thyrotropin-Releasing Hormone / pharmacology
  • Trans-Activators*
  • Transcriptional Regulator ERG
  • Transfection
  • Type C Phospholipases / metabolism*
  • Xenopus

Substances

  • Cation Transport Proteins
  • DNA-Binding Proteins
  • ERG protein, human
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • KCNH6 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Receptors, Thyrotropin-Releasing Hormone
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Thyrotropin-Releasing Hormone
  • Type C Phospholipases