title: Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells.
abstract: Carotid body chemoreceptors sense hypoxemia, hypercapnia, and acidosis and play an important role in cardiorespiratory regulation. The molecular mechanism of pH sensing by chemoreceptors is not clear, although it has been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K+ current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using the whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward current in glomus cells that was inhibited by the acid-sensing ion channel (ASIC) blocker amiloride, absent in Na+-free bathing solution, and enhanced by either Ca2+-free buffer or addition of lactate. In addition, ASIC1 and ASIC3 were shown to be expressed in rat carotid body by quantitative PCR and immunohistochemistry. In the current-clamp mode, extracellular acidosis evoked both a transient and sustained depolarizations. The initial transient component of depolarization was blocked by amiloride, whereas the sustained component was eliminated by removal of K+ from the pipette solution and partially blocked by the TASK (tandem-p-domain, acid-sensitive K+ channel) blockers anandamide and quinidine. The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels.
authors.affiliation: Cardiovascular Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Tan
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Lu
authors.forename: Carol A
authors.initials: CA
authors.lastname: Whiteis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Benson
authors.forename: Mark W
authors.initials: MW
authors.lastname: Chapleau
authors.forename: Francois M
authors.initials: FM
authors.lastname: Abboud
mesh_terms: D062565:Acid Sensing Ion Channels; D000138:Acidosis / Q000503:physiopathology*; D000143:Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002344:Carotid Body / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D000143:Acids; C568268:Asic1 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium