title: Hypotonic stimuli enhance proton-gated currents of acid-sensing ion channel-1b.
abstract: Acid-sensing ion channels (ASICs) are strong candidates for mammalian mechanoreceptors. We investigated whether mouse acid-sensing ion channel-1b (ASIC1b) is sensitive to mechanical stimuli using oocyte electrophysiology, because ASIC1b is located in the mechanosensory stereocilia of cochlear hair cells. Hypotonic stimuli that induced membrane stretch of oocytes evoked no significant current in ASIC1b-expressing oocytes at pH 7.5. However, acid (pH 4.0 or 5.0)-evoked currents in the oocytes were substantially enhanced by the hypotonicity, showing mechanosensitivity of ASIC1b and possible mechanogating of the channel in the presence of other components. Interestingly, the ASIC1b channel was permeable to K(+) (a principal charge carrier for cochlear sensory transduction) and the affinity of the channel for amiloride (IC(50) (inhibition constant)=approximately 48.3 microM) was quite similar to that described for the mouse hair cell mechanotransducer current. Taken together, these data raise the possibility that ASIC1b participates in cochlear mechanoelectrical transduction.
authors.affiliation: Department of Neurobiology and Anatomy, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ugawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ishida
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Shoichi
authors.initials: S
authors.lastname: Shimada
mesh_terms: D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D007038:Hypotonic Solutions / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011522:Protons; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D007038:Hypotonic Solutions; D007473:Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011522:Protons; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride