RGD Reference Report - Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. - Rat Genome Database

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

Authors: Sutherland, S P  Benson, C J  Adelman, J P  McCleskey, E W 
Citation: Sutherland SP, etal., Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):711-6. doi: 10.1073/pnas.98.2.711. Epub 2000 Dec 19.
RGD ID: 596936209
Pubmed: PMID:11120882   (View Abstract at PubMed)
PMCID: PMC14653   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.98.2.711   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Asic3Ratdetection of chemical stimulus involved in sensory perception of pain involved_inIDA PMID:11120882UniProt 
Asic3Ratmembrane depolarization involved_inIDA PMID:11120882UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Asic3RatpH-gated calcium channel activity enablesIDA PMID:11120882UniProt 
Asic3RatpH-gated sodium channel activity enablesIDA PMID:11120882UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Asic3  (acid sensing ion channel subunit 3)


Additional Information