Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells

Zhi-Yong Tan; Yongjun Lu; Carol A Whiteis; Christopher J Benson; Mark W Chapleau; Francois M Abboud

doi:10.1161/CIRCRESAHA.107.154377

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Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells

Journal article

Open access

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Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells

Zhi-Yong Tan, Yongjun Lu, Carol A Whiteis, Christopher J Benson, Mark W Chapleau and Francois M Abboud

Circulation research, Vol.101(10), pp.1009-1019

11/09/2007

DOI: 10.1161/CIRCRESAHA.107.154377

PMID: 17872465

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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.

Sodium Channels - physiology

RNA, Messenger - metabolism

Acids - metabolism

Extracellular Space - metabolism

Ion Channel Gating - physiology

Membrane Proteins - physiology

Acidosis - physiopathology

Sodium - pharmacokinetics

Acids - pharmacology

Carotid Body - physiology

Membrane Potentials - drug effects

Nerve Tissue Proteins - physiology

Acid Sensing Ion Channels

Membrane Proteins - genetics

Rats

Chemoreceptor Cells - physiology

Membrane Potentials - physiology

Nerve Tissue Proteins - genetics

Potassium - pharmacokinetics

Stimulation, Chemical

Patch-Clamp Techniques

Animals

Sodium Channels - genetics

Calcium - pharmacokinetics

Hydrogen-Ion Concentration

Ion Channel Gating - drug effects

Details

Title: Subtitle: Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells
Creators: Zhi-Yong Tan - Cardiovascular Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
Yongjun Lu
Carol A Whiteis
Christopher J Benson
Mark W Chapleau
Francois M Abboud
Resource Type: Journal article
Publication Details: Circulation research, Vol.101(10), pp.1009-1019
DOI: 10.1161/CIRCRESAHA.107.154377
PMID: 17872465
NLM abbreviation: Circ Res
ISSN: 0009-7330
eISSN: 1524-4571
Publisher: United States
Grant note: HL14388-36 / NHLBI NIH HHS
Language: English
Date published: 11/09/2007
Academic Unit: Molecular Physiology and Biophysics; Critical Care; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
Record Identifier: 9984025352902771

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