An acid-sensing ion channel that detects ischemic pain
| Autor: | E.W. McCleskey, L.A. Naves |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Physiology
Acid-sensing ion channels Immunology Biophysics Ischemia Pain Nerve Tissue Proteins Sensory system Biochemistry Sodium Channels chemistry.chemical_compound Dorsal root ganglion medicine Extracellular Animals Lactic Acid Neurons Afferent General Pharmacology Toxicology and Pharmaceutics Dorsal root ganglia lcsh:QH301-705.5 Acid-sensing ion channel Acidosis lcsh:R5-920 Lactic acidosis Chemistry General Neuroscience Membrane Proteins Cell Biology General Medicine Hydrogen-Ion Concentration medicine.disease Rats Lactic acid Acid Sensing Ion Channels medicine.anatomical_structure lcsh:Biology (General) Anesthesia medicine.symptom lcsh:Medicine (General) |
| Zdroj: | Brazilian Journal of Medical and Biological Research v.38 n.11 2005 Brazilian Journal of Medical and Biological Research Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC Brazilian Journal of Medical and Biological Research, Vol 38, Iss 11, Pp 1561-1569 (2005) Brazilian Journal of Medical and Biological Research, Volume: 38, Issue: 11, Pages: 1561-1569, Published: NOV 2005 |
| ISSN: | 0100-879X |
| Popis: | Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (approximately 40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia. |
| Databáze: | OpenAIRE |
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