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

S. P. Sutherland, C. J. Benson, John Adelman, E. W. McCleskey

Research output: Contribution to journalArticle

307 Citations (Scopus)

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 Ca2+, 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.

Original languageEnglish (US)
Pages (from-to)711-716
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number2
DOIs
StatePublished - Jan 16 2001

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Acid Sensing Ion Channels
Ischemia
Neurons
Acids
Degenerin Sodium Channels
Epithelial Sodium Channels
Afferent Neurons
Pain
Aptitude
Caenorhabditis elegans
Sensory Receptor Cells
Ion Channels
Action Potentials
Myocardial Ischemia
Protons
Myocardial Infarction
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. / Sutherland, S. P.; Benson, C. J.; Adelman, John; McCleskey, E. W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 2, 16.01.2001, p. 711-716.

Research output: Contribution to journalArticle

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