Oxidation of a potassium channel causes progressive sensory function loss during aging

Nat Neurosci. 2009 May;12(5):611-7. doi: 10.1038/nn.2291. Epub 2009 Mar 29.

Abstract

Potassium channels are key regulators of neuronal excitability. Here we show that oxidation of the K(+) channel KVS-1 during aging causes sensory function loss in Caenorhabditis elegans and that protection of this channel from oxidation preserves neuronal function. Chemotaxis, a function controlled by KVS-1, was significantly impaired in worms exposed to oxidizing agents, but only moderately affected in worms harboring an oxidation-resistant KVS-1 mutant (C113S). In aging C113S transgenic worms, the effects of free radical accumulation were significantly attenuated compared to those in wild type. Electrophysiological analyses showed that both reactive oxygen species (ROS) accumulation during aging and acute exposure to oxidizing agents acted primarily to alter the excitability of the neurons that mediate chemotaxis. Together, these findings establish a pivotal role for ROS-mediated oxidation of voltage-gated K(+) channels in sensorial decline during aging in invertebrates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Animals, Genetically Modified
  • CHO Cells
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chemotaxis / physiology
  • Cricetinae
  • Cricetulus
  • Free Radicals / metabolism
  • Nervous System / cytology
  • Nervous System / metabolism*
  • Oxidative Stress / physiology*
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Reactive Oxygen Species / metabolism
  • Sensation Disorders / genetics
  • Sensation Disorders / metabolism*
  • Sensation Disorders / physiopathology
  • Sensory Receptor Cells / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Free Radicals
  • KVS-1 protein, C elegans
  • Potassium Channels, Voltage-Gated
  • Reactive Oxygen Species