Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1

J Biol Chem. 2008 Mar 28;283(13):8634-42. doi: 10.1074/jbc.M709304200. Epub 2008 Jan 25.


The Shaker family voltage-dependent potassium channels (Kv1) assemble with cytosolic beta-subunits (Kvbeta) to form a stable complex. All Kvbeta subunits have a conserved core domain, which in one of them (Kvbeta2) is an aldoketoreductase that utilizes NADPH as a cofactor. In addition to this core, Kvbeta1 has an N terminus that closes the channel by the N-type inactivation mechanism. Point mutations in the putative catalytic site of Kvbeta1 alter the on-rate of inactivation. Whether the core of Kvbeta1 functions as an enzyme and whether its enzymatic activity affects N-type inactivation had not been explored. Here, we show that Kvbeta1 is a functional aldoketoreductase and that oxidation of the Kvbeta1-bound cofactor, either enzymatically by a substrate or non-enzymatically by hydrogen peroxide or NADP(+), induces a large increase in open channel current. The modulation is not affected by deletion of the distal C terminus of the channel, which has been suggested in structural studies to interact with Kvbeta. The rate of increase in current, which reflects NADPH oxidation, is approximately 2-fold faster at 0-mV membrane potential than at -100 mV. Thus, cofactor oxidation by Kvbeta1 is regulated by membrane potential, presumably via voltage-dependent structural changes in Kv1.1 channels.

Publication types

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

MeSH terms

  • Aldehyde Reductase / genetics
  • Aldehyde Reductase / metabolism*
  • Animals
  • Electrophysiology
  • Enzyme Activation
  • Female
  • Gene Deletion
  • Hydrogen Peroxide / pharmacology
  • Ion Channel Gating
  • NADP / metabolism
  • Oocytes
  • Oxidation-Reduction / drug effects
  • Patch-Clamp Techniques
  • Protein Binding
  • Rats
  • Shaker Superfamily of Potassium Channels / genetics
  • Shaker Superfamily of Potassium Channels / metabolism*
  • Substrate Specificity
  • Xenopus laevis


  • Shaker Superfamily of Potassium Channels
  • NADP
  • Hydrogen Peroxide
  • Aldehyde Reductase

Associated data

  • RefSeq/NM_017303