Acid sensing ionic channels: modulation by redox reagents

Biochim Biophys Acta. 2005 Aug 15;1745(1):1-6. doi: 10.1016/j.bbamcr.2005.01.008. Epub 2005 Feb 24.

Abstract

Acid-sensing ion channels (ASICs) are widely expressed in mammalian sensory neurons and supposedly play a role in nociception and acid sensing. In the course of functioning the redox status of the tissue is subjected to changes. Using whole-cell patch-clamp/concentration clamp techniques we have investigated the effect of redox reagents on the ASIC-like currents in the sensory ganglia and hippocampal neurons of rat. The reducing agent dithiothreitol (DTT), when applied in the concentrations 1-2 mM, reversibly potentiates proton-activated currents, while the oxidizing reagent 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) causes their inhibition. The EC50 and Hill coefficient for the activation of ASIC-like currents by protons are not affected by DTT. Redox modulation of proton-activated currents is independent on the membrane potential and on the level of pH used for the current activation. The endogenous antioxidant tripeptide glutathione (its reduced form, g-l-glutamyl-l-cysteinyl-glycine, GSH) also potentiates proton-activated currents. Our results indicate that ASIC-like currents are susceptible to regulation by redox agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Animals
  • Calcium / metabolism
  • Dithionitrobenzoic Acid / pharmacology
  • Glutathione / pharmacology
  • Hippocampus / physiology*
  • Hydrogen-Ion Concentration*
  • Indicators and Reagents
  • Membrane Proteins / drug effects
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology*
  • Oxidation-Reduction
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Sodium Channels / drug effects
  • Sodium Channels / physiology*

Substances

  • Acid Sensing Ion Channels
  • Indicators and Reagents
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Sodium Channels
  • Dithionitrobenzoic Acid
  • Sodium
  • Glutathione
  • Calcium