An acid-sensing ion channel that detects ischemic pain


Autoria(s): Naves,L.A.; McCleskey,E.W.
Data(s)

01/11/2005

Resumo

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 (~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.

Formato

text/html

Identificador

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005001100001

Idioma(s)

en

Publicador

Associação Brasileira de Divulgação Científica

Fonte

Brazilian Journal of Medical and Biological Research v.38 n.11 2005

Palavras-Chave #Pain #Ischemia #Dorsal root ganglia #Acid-sensing ion channels #Lactic acidosis
Tipo

journal article