Characterization of Acid-Sensing Ion Channels in Dorsal Horn Neurons of Rat Spinal Cord

J Biol Chem. 2004 Oct 15;279(42):43716-24. doi: 10.1074/jbc.M403557200. Epub 2004 Aug 9.

Abstract

Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. In periphery, they contribute to sensory transmission, including that of nociception and pain. Here we characterized ASIC-like currents in dorsal horn neurons of the rat spinal cord and their functional modulation in pathological conditions. Reverse transcriptase-nested PCR and Western blotting showed that three ASIC isoforms, ASIC1a, ASIC2a, and ASIC2b, are expressed at a high level in dorsal horn neurons. Electrophysiological and pharmacological properties of the proton-gated currents suggest that homomeric ASIC1a and/or heteromeric ASIC1a + 2b channels are responsible for the proton-induced currents in the majority of dorsal horn neurons. Acidification-induced action potentials in these neurons were compatible in a pH-dependent manner with the pH dependence of ASIC-like current. Furthermore, peripheral complete Freund's adjuvant-induced inflammation resulted in increased expression of both ASIC1a and ASIC2a in dorsal horn. These results support the idea that the ASICs of dorsal horn neurons participate in central sensory transmission/modulation under physiological conditions and may play important roles in inflammation-related persistent pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Animals
  • Cations, Divalent / pharmacology
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology
  • Electrophysiology
  • Ganglia, Spinal / physiology
  • Hydrogen-Ion Concentration
  • Inflammation / genetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons, Afferent / physiology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / physiology*
  • Rats
  • Sodium Channels / genetics
  • Sodium Channels / physiology*
  • Spinal Cord / physiology
  • Synaptic Transmission / physiology
  • Tetrodotoxin / pharmacology
  • Transcription, Genetic

Substances

  • Acid Sensing Ion Channels
  • Cations, Divalent
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Sodium Channels
  • Tetrodotoxin