Angiotensin receptor type 1 forms a complex with the transient outward potassium channel Kv4.3 and regulates its gating properties and intracellular localization

J Biol Chem. 2004 Nov 12;279(46):48231-7. doi: 10.1074/jbc.M405789200. Epub 2004 Sep 1.

Abstract

We report a novel signal transduction complex of the angiotensin receptor type 1. In this complex the angiotensin receptor type 1 associates with the potassium channel alpha-subunit Kv4.3 and regulates its intracellular distribution and gating properties. Co-localization of Kv4.3 with angiotensin receptor type 1 and fluorescent resonance energy transfer between those two proteins labeled with cyan and yellow-green variants of green fluorescent protein revealed that Kv4.3 and angiotensin receptor type I are located in close proximity to each other in the cell. The angiotensin receptor type 1 also co-immunoprecipitates with Kv4.3 from canine ventricle or when co-expressed with Kv4.3 and its beta-subunit KChIP2 in human embryonic kidney 293 cells. Treatment of the cells with angiotensin II results in the internalization of Kv4.3 in a complex with the angiotensin receptor type 1. When stimulated with angiotensin II, angiotensin receptors type 1 modulate gating properties of the remaining Kv4.3 channels on the cell surface by shifting their activation voltage threshold to more positive values. We hypothesize that the angiotensin receptor type 1 provides its internalization molecular scaffold to Kv4.3 and in this way regulates the cell surface representation of the ion channel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Dogs
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Dyes / metabolism
  • Humans
  • Kv Channel-Interacting Proteins
  • Macromolecular Substances
  • Myocardium / cytology
  • Myocardium / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Protein Subunits / metabolism
  • Rats
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Shal Potassium Channels
  • Signal Transduction / physiology*
  • Transport Vesicles / chemistry
  • Transport Vesicles / metabolism

Substances

  • Calcium-Binding Proteins
  • Fluorescent Dyes
  • KCND3 protein, human
  • KCNIP2 protein, human
  • Kcnd3 protein, rat
  • Kcnip2 protein, rat
  • Kv Channel-Interacting Proteins
  • Macromolecular Substances
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Receptor, Angiotensin, Type 1
  • Recombinant Fusion Proteins
  • Shal Potassium Channels
  • Angiotensin II