An acid-sensing ion channel that detects ischemic pain
Braz. j. med. biol. res
;
38(11): 1561-1569, Nov. 2005. ilus
Artículo
en Inglés
| LILACS
| ID: lil-414709
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 percent) 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.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Dolor
/
Canales de Sodio
/
Ácido Láctico
/
Isquemia
/
Proteínas de la Membrana
/
Proteínas del Tejido Nervioso
/
Neuronas Aferentes
Límite:
Animales
Idioma:
Inglés
Revista:
Braz. j. med. biol. res
Asunto de la revista:
Biologia
/
Medicina
Año:
2005
Tipo del documento:
Artículo
/
Congreso y conferencia
País de afiliación:
Brasil
/
Estados Unidos
Institución/País de afiliación:
Oregon Health Science University/US
/
Universidade Federal de Minas Gerais/BR
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