Oxidation of NADPH on Kvbeta1 inhibits ball-and-chain type inactivation by restraining the chain

Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5885-90. doi: 10.1073/pnas.1100316108. Epub 2011 Mar 21.


The Kv1 family voltage-dependent K(+) channels assemble with cytosolic β subunits (Kvβ), which are composed of a flexible N terminus followed by a structured core domain. The N terminus of certain Kvβs inactivates the channel by blocking the ion conduction pore, and the core domain is a functional enzyme that uses NADPH as a cofactor. Oxidation of the Kvβ-bound NADPH inhibits inactivation and potentiates channel current, but the mechanism behind this effect is unknown. Here we show that after oxidation, the core domain binds to part of the N terminus, thus restraining it from blocking the channel. The interaction is partially mediated by two negatively charged residues on the core domain and three positively charged ones on the N terminus. These results provide a molecular basis for the coupling between the cellular redox state and channel activity, and establish Kvβ as a target for pharmacological control of Kv1 channels.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Cloning, Molecular
  • DNA Primers / genetics
  • Electrophysiology
  • Genetic Vectors
  • Kv1.1 Potassium Channel / genetics
  • Kv1.1 Potassium Channel / metabolism*
  • NADP / metabolism*
  • Oxidation-Reduction
  • Polymerase Chain Reaction
  • Rats
  • Sequence Analysis, DNA
  • Spectrometry, Fluorescence


  • DNA Primers
  • Kv1.1 Potassium Channel
  • NADP