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An acid-sensing ion channel that detects ischemic pain.
Naves, L A; McCleskey, E W.
Afiliación
  • Naves LA; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. lnaves@icb.ufmg.br
Braz J Med Biol Res ; 38(11): 1561-9, 2005 Nov.
Article en En | MEDLINE | ID: mdl-16258623
ABSTRACT
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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Canales de Sodio / Ácido Láctico / Isquemia / Proteínas de la Membrana / Proteínas del Tejido Nervioso / Neuronas Aferentes Límite: Animals Idioma: En Revista: Braz J Med Biol Res Año: 2005 Tipo del documento: Article País de afiliación: Brasil
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Canales de Sodio / Ácido Láctico / Isquemia / Proteínas de la Membrana / Proteínas del Tejido Nervioso / Neuronas Aferentes Límite: Animals Idioma: En Revista: Braz J Med Biol Res Año: 2005 Tipo del documento: Article País de afiliación: Brasil