Heterologous Multimeric Assembly Is Essential for K+ Channel Activity of Neuronal and Cardiac G-protein-activated Inward Rectifiers

Biochem Biophys Res Commun. 1995 Jul 17;212(2):657-63. doi: 10.1006/bbrc.1995.2019.

Abstract

The family of G-protein-activated inward-rectifiers K+ channels presently comprise at least 3 cloned members called GIRK1, GIRK2 and GIRK3. A close structural parent of GIRK channels has recently been described as being an ATP-sensitive K+ channel. This paper shows that Xenopus expression of this new channel that we call GIRK4 does not produce an ATP-inhibitable activity with a pharmacological activation by pinacidil as previously described but instead a G-protein activated inward-rectifier. While oocyte expression of single subunits is infrequent and relatively modest in intensity, expression of GIRK1,2, GIRK1,4 and GIRK2,4 mixtures leads to routine and robust expression of K+ channels indicating that heterologous subunit assembly is necessary for activity. Activity of GIRK1,2, GIRK1,4 and GIRK2,4 channels required the presence of ATP acting as an activator at the cytoplasmic face and is further activated by the beta gamma subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Electric Conductivity
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins / physiology*
  • Gene Expression
  • Gene Transfer Techniques
  • Heart / physiology*
  • Macromolecular Substances
  • Neurons / physiology*
  • Oocytes / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Inwardly Rectifying*
  • RNA, Complementary
  • Structure-Activity Relationship
  • Xenopus

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Macromolecular Substances
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • RNA, Complementary
  • Adenosine Triphosphate
  • GTP-Binding Proteins