Sensing muscle ischemia: Coincident detection of acid and ATP via interplay of two ion channels

William T. Birdsong, Leonardo Fierro, Frank G. Williams, Valeria Spelta, Ligia A. Naves, Michelle Knowles, Josephine Marsh-Haffner, John Adelman, Wolfhard Almers, Robert P. Elde, Edwin W. McCleskey

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)739-749
Number of pages11
JournalNeuron
Volume68
Issue number4
DOIs
StatePublished - Nov 18 2010

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Adenine Nucleotides
Ion Channels
Ischemia
Sensory Receptor Cells
Pain
Muscles
Acids
Acid Sensing Ion Channels
Lactic Acidosis
Acidosis
Chest Pain
Lactic Acid
Leg
Myocardial Infarction
Oxygen

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Birdsong, W. T., Fierro, L., Williams, F. G., Spelta, V., Naves, L. A., Knowles, M., ... McCleskey, E. W. (2010). Sensing muscle ischemia: Coincident detection of acid and ATP via interplay of two ion channels. Neuron, 68(4), 739-749. https://doi.org/10.1016/j.neuron.2010.09.029

Sensing muscle ischemia : Coincident detection of acid and ATP via interplay of two ion channels. / Birdsong, William T.; Fierro, Leonardo; Williams, Frank G.; Spelta, Valeria; Naves, Ligia A.; Knowles, Michelle; Marsh-Haffner, Josephine; Adelman, John; Almers, Wolfhard; Elde, Robert P.; McCleskey, Edwin W.

In: Neuron, Vol. 68, No. 4, 18.11.2010, p. 739-749.

Research output: Contribution to journalArticle

Birdsong, WT, Fierro, L, Williams, FG, Spelta, V, Naves, LA, Knowles, M, Marsh-Haffner, J, Adelman, J, Almers, W, Elde, RP & McCleskey, EW 2010, 'Sensing muscle ischemia: Coincident detection of acid and ATP via interplay of two ion channels', Neuron, vol. 68, no. 4, pp. 739-749. https://doi.org/10.1016/j.neuron.2010.09.029
Birdsong WT, Fierro L, Williams FG, Spelta V, Naves LA, Knowles M et al. Sensing muscle ischemia: Coincident detection of acid and ATP via interplay of two ion channels. Neuron. 2010 Nov 18;68(4):739-749. https://doi.org/10.1016/j.neuron.2010.09.029
Birdsong, William T. ; Fierro, Leonardo ; Williams, Frank G. ; Spelta, Valeria ; Naves, Ligia A. ; Knowles, Michelle ; Marsh-Haffner, Josephine ; Adelman, John ; Almers, Wolfhard ; Elde, Robert P. ; McCleskey, Edwin W. / Sensing muscle ischemia : Coincident detection of acid and ATP via interplay of two ion channels. In: Neuron. 2010 ; Vol. 68, No. 4. pp. 739-749.
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