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

Academic Article

Abstract

  • 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.
  • Authors

  • Chen, Xuanmao
  • GrĂ¼nder, Stefan
  • Status

    Publication Date

  • March 15, 2007
  • Published In

    Keywords

  • Acid Sensing Ion Channels
  • Acids
  • Animals
  • Calcium
  • Endocytosis
  • Female
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Ion Channel Gating
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Oocytes
  • Patch-Clamp Techniques
  • Protons
  • Rats
  • Sodium Channels
  • Tachyphylaxis
  • Xenopus laevis
  • Digital Object Identifier (doi)

    Start Page

  • 657
  • End Page

  • 670
  • Volume

  • 579
  • Issue

  • Pt 3