Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a

J Physiol. 2007 Mar 15;579(Pt 3):657-70. doi: 10.1113/jphysiol.2006.120733. Epub 2007 Jan 4.


The homomeric acid-sensing ion channel 1a (ASIC1a) is a H+-activated ion channel with important physiological functions and pathophysiological impact in the central nervous system. Here we show that homomeric ASIC1a is distinguished from other ASICs by a reduced response to successive acid stimulations. Such a reduced response is called tachyphylaxis. We show that tachyphylaxis depends on H+ permeating through ASIC1a, that tachyphylaxis is attenuated by extracellular Ca2+, and that tachyphylaxis is probably linked to Ca2+ permeability of ASIC1a. Moreover, we provide evidence that tachyphylaxis is probably due to a long-lived inactive state of ASIC1a. A deeper understanding of ASIC1a tachyphylaxis may lead to pharmacological control of ASIC1a activity that could be of potential benefit for the treatment of stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Acids / pharmacology*
  • Animals
  • Calcium / pharmacokinetics
  • Endocytosis / physiology
  • Female
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Ion Channel Gating / physiology
  • Membrane Proteins / chemistry*
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / physiology*
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Protons
  • Rats
  • Sodium Channels / chemistry*
  • Sodium Channels / physiology*
  • Tachyphylaxis / physiology*
  • Xenopus laevis


  • Acid Sensing Ion Channels
  • Acids
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protons
  • Sodium Channels
  • Calcium