K(V)LQT1 and lsK (minK) Proteins Associate to Form the I(Ks) Cardiac Potassium Current

Nature. 1996 Nov 7;384(6604):78-80. doi: 10.1038/384078a0.

Abstract

In mammalian cardiac cells, a variety of transient or sustained K+ currents contribute to the repolarization of action potentials. There are two main components of the delayed-rectifier sustained K+ current, I(Kr) (rapid) and I(Ks), (slow). I(Kr) is the product of the gene HERG, which is altered in the long-QT syndrome, LQT2. A channel with properties similar to those of the I(Ks) channel is produced when the cardiac protein IsK is expressed in Xenopus oocytes. However, it is a small protein with a very unusual structure for a cation channel. The LQT1 gene is another gene associated with the LQT syndrome, a disorder that causes sudden death from ventricular arrhythmias. Here we report the cloning of the full-length mouse K(V)LQT1 complementary DNA and show that K(V)LQT1 associates with IsK to form the channel underlying the I(Ks) cardiac current, which is a target of class-III anti-arrhythmic drugs and is involved in the LQT1 syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cation Transport Proteins*
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins*
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Humans
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Mice
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Point Mutation
  • Potassium / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcriptional Regulator ERG
  • Transfection
  • 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
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Kcnq1 protein, mouse
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Trans-Activators
  • Transcriptional Regulator ERG
  • potassium channel protein I(sk)
  • Potassium

Associated data

  • GENBANK/U70068