Oxidative modulation of voltage-gated potassium channels

Antioxid Redox Signal. 2014 Aug 20;21(6):933-52. doi: 10.1089/ars.2013.5614. Epub 2013 Oct 26.

Abstract

Significance: Voltage-gated K+ channels are a large family of K+-selective ion channel protein complexes that open on membrane depolarization. These K+ channels are expressed in diverse tissues and their function is vital for numerous physiological processes, in particular of neurons and muscle cells. Potentially reversible oxidative regulation of voltage-gated K+ channels by reactive species such as reactive oxygen species (ROS) represents a contributing mechanism of normal cellular plasticity and may play important roles in diverse pathologies including neurodegenerative diseases.

Recent advances: Studies using various protocols of oxidative modification, site-directed mutagenesis, and structural and kinetic modeling provide a broader phenomenology and emerging mechanistic insights.

Critical issues: Physicochemical mechanisms of the functional consequences of oxidative modifications of voltage-gated K+ channels are only beginning to be revealed. In vivo documentation of oxidative modifications of specific amino-acid residues of various voltage-gated K+ channel proteins, including the target specificity issue, is largely absent.

Future directions: High-resolution chemical and proteomic analysis of ion channel proteins with respect to oxidative modification combined with ongoing studies on channel structure and function will provide a better understanding of how the function of voltage-gated K+ channels is tuned by ROS and the corresponding reducing enzymes to meet cellular needs.

Publication types

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

MeSH terms

  • Animals
  • Ether-A-Go-Go Potassium Channels / chemistry
  • Ether-A-Go-Go Potassium Channels / genetics
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Humans
  • KCNQ Potassium Channels / chemistry
  • KCNQ Potassium Channels / genetics
  • KCNQ Potassium Channels / metabolism
  • Large-Conductance Calcium-Activated Potassium Channels / chemistry
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Multigene Family
  • Oxidation-Reduction*
  • Potassium Channels, Voltage-Gated / chemistry
  • Potassium Channels, Voltage-Gated / classification
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*

Substances

  • Ether-A-Go-Go Potassium Channels
  • KCNQ Potassium Channels
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Voltage-Gated