title: Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.
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.affiliation: Department of Physiology II, Röntgenring 9, 97070 Würzburg, Germany.
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Chen
authors.forename: Stefan
authors.initials: S
authors.lastname: Gründer
mesh_terms: D062565:Acid Sensing Ion Channels; D000143:Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D004705:Endocytosis / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011522:Protons; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry* / Q000502:physiology*; D013618:Tachyphylaxis / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D062565:Acid Sensing Ion Channels; D000143:Acids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D015222:Sodium Channels; D002118:Calcium