| Sensing muscle ischemia: coincident detection of acid and ATP via interplay of two ion channels. | |
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MedLine Citation:
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PMID: 21092862 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ischemic pain--examples include the chest pain of a heart attack and the leg pain of a 30 s sprint--occurs when muscle gets too little oxygen for its metabolic need. Lactic acid cannot act alone to trigger ischemic pain because the pH change is so small. Here, we show that another compound released from ischemic muscle, adenosine tri-phosphate (ATP), works together with acid by increasing the pH sensitivity of acid-sensing ion channel number 3 (ASIC3), the molecule used by sensory neurons to detect lactic acidosis. Our data argue that ATP acts by binding to P2X receptors that form a molecular complex with ASICs; the receptor on sensory neurons appears to be P2X5, an electrically quiet ion channel. Coincident detection of acid and ATP should confer sensory selectivity for ischemia over other conditions of acidosis. |
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Authors:
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William T Birdsong; Leonardo Fierro; Frank G Williams; Valeria Spelta; Ligia A Naves; Michelle Knowles; Josephine Marsh-Haffner; John P Adelman; Wolfhard Almers; Robert P Elde; Edwin W McCleskey |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuron Volume: 68 ISSN: 1097-4199 ISO Abbreviation: Neuron Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-01-06 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 739-49 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Vollum Institute, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acidosis, Lactic
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metabolism,
physiopathology Adenosine Triphosphate / metabolism*, physiology Amino Acid Sequence Animals CHO Cells COS Cells Cercopithecus aethiops Cricetinae Cricetulus HEK293 Cells Humans Hydrogen-Ion Concentration Ischemia / metabolism*, physiopathology Molecular Sequence Data Muscle, Skeletal / blood supply*, innervation*, metabolism Rats Rats, Sprague-Dawley Receptors, Purinergic P2X5 / metabolism*, physiology Sensory Receptor Cells / metabolism*, pathology, physiology Sodium Channels / metabolism*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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HL64840/HL/NHLBI NIH HHS; NS37010/NS/NINDS NIH HHS; R01 HL064840-05/HL/NHLBI NIH HHS; R01 NS037010-08/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ACCN3 protein, human; 0/Receptors, Purinergic P2X5; 0/Sodium Channels; 56-65-5/Adenosine Triphosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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