Stoichiometry of the KCNQ1 - KCNE1 ion channel complex

Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18862-7. doi: 10.1073/pnas.1010354107. Epub 2010 Oct 20.

Abstract

The KCNQ1 voltage-gated potassium channel and its auxiliary subunit KCNE1 play a crucial role in the regulation of the heartbeat. The stoichiometry of KCNQ1 and KCNE1 complex has been debated, with some results suggesting that the four KCNQ1 subunits that form the channel associate with two KCNE1 subunits (a 42 stoichiometry), while others have suggested that the stoichiometry may not be fixed. We applied a single molecule fluorescence bleaching method to count subunits in many individual complexes and found that the stoichiometry of the KCNQ1 - KCNE1 complex is flexible, with up to four KCNE1 subunits associating with the four KCNQ1 subunits of the channel (a 44 stoichiometry). The proportion of the various stoichiometries was found to depend on the relative expression densities of KCNQ1 and KCNE1. Strikingly, both the voltage-dependence and kinetics of gating were found to depend on the relative densities of KCNQ1 and KCNE1, suggesting the heart rhythm may be regulated by the relative expression of the auxiliary subunit and the resulting stoichiometry of the channel complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Ion Channel Gating / physiology
  • KCNQ1 Potassium Channel / genetics
  • KCNQ1 Potassium Channel / metabolism*
  • Mice
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Myocardial Contraction / physiology*
  • Myocardium / metabolism*
  • Oocytes
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Rats
  • Xenopus laevis

Substances

  • KCNE1 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Kcne1 protein, mouse
  • Kcne1 protein, rat
  • Kcnq1 protein, mouse
  • Kcnq1 protein, rat
  • Multiprotein Complexes
  • Potassium Channels, Voltage-Gated