Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.
Neuron
; 37(1): 75-84, 2003 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-12526774
ABSTRACT
Acid-sensing ion channels (ASICs) open when extracellular pH drops and they are enhanced by lactate, making them specialized for detecting lactic acidosis. Highly expressed on cardiac nociceptors and some other sensory neurons, ASICs may help trigger pain caused by tissue ischemia. We report that H(+) opens ASIC3 by speeding release of Ca(2+) from a high-affinity binding site (K(Ca) = 150 nM) on the extracellular side of the pore. The bound Ca(2+) blocks permeation and the channel conducts when multiple H(+) ions relieve this block. Activation through Ca(2+) explains sensitivity to lactate, which decreases extracellular [Ca(2+)], and it may prove relevant in CNS pathologies (stroke, seizure) that simultaneously drop pH and Ca(2+).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prótons
/
Canais de Sódio
/
Membrana Celular
/
Células Quimiorreceptoras
/
Cálcio
/
Sinalização do Cálcio
/
Proteínas de Membrana
/
Proteínas do Tecido Nervoso
/
Neurônios Aferentes
Limite:
Animals
Idioma:
En
Revista:
Neuron
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos