Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons

Stephani P Sutherland; Christopher J Benson; John P Adelman; Edwin W McCleskey

doi:10.1073/pnas.98.2.711

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Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons

Journal article

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Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons

Stephani P Sutherland, Christopher J Benson, John P Adelman and Edwin W McCleskey

Proceedings of the National Academy of Sciences - PNAS, Vol.98(2), pp.711-716

From the Cover

01/16/2001

DOI: 10.1073/pnas.98.2.711

PMCID: PMC14653

PMID: 11120882

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Abstract

Cardiac afferents are sensory neurons that mediate angina, pain that occurs when the heart receives insufficient blood supply for its metabolic demand (ischemia). These neurons display enormous acid-evoked depolarizing currents, and they fire action potentials in response to extracellular acidification that accompanies myocardial ischemia. Here we show that acid-sensing ion channel 3 (ASIC3), but no other known acid-sensing ion channel, reproduces the functional features of the channel that underlies the large acid-evoked current in cardiac afferents. ASIC3 and the native channel are both especially sensitive to pH, interact similarly with Ca 2+ , and gate rapidly between closed, open, and desensitized states. Particularly important is the ability of ASIC3 and the native channel to open at pH 7, a value reached in the first few minutes of a heart attack. The steep activation curve suggests that the channel opens when four protons bind. We propose that ASIC3, a member of the degenerin channel (of Caenorhabditis elegans )/epithelial sodium channel family of ion channels, is the sensor of myocardial acidity that triggers cardiac pain, and that it might be a useful pharmaceutical target for treating angina.

Biological Sciences

Details

Title: Subtitle: Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons
Creators: Stephani P Sutherland - The Vollum Institute, Oregon Health Sciences University, Portland, OR 97201-3098
Christopher J Benson - The Vollum Institute, Oregon Health Sciences University, Portland, OR 97201-3098
John P Adelman - The Vollum Institute, Oregon Health Sciences University, Portland, OR 97201-3098
Edwin W McCleskey - The Vollum Institute, Oregon Health Sciences University, Portland, OR 97201-3098
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.98(2), pp.711-716
Series: From the Cover
DOI: 10.1073/pnas.98.2.711
PMID: 11120882
PMCID: PMC14653
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 01/16/2001
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040438302771

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