An acid-sensing ion channel that detects ischemic pain
Braz. j. med. biol. res
;
38(11): 1561-1569, Nov. 2005. ilus
Artigo
em Inglês
| 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:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Dor
/
Canais de Sódio
/
Ácido Láctico
/
Isquemia
/
Proteínas de Membrana
/
Proteínas do Tecido Nervoso
/
Neurônios Aferentes
Limite:
Animais
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2005
Tipo de documento:
Artigo
/
Congresso e conferência
País de afiliação:
Brasil
/
Estados Unidos
Instituição/País de afiliação:
Oregon Health Science University/US
/
Universidade Federal de Minas Gerais/BR
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