Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors innervating the guinea pig esophagus.
Neurogastroenterol Motil
; 27(6): 865-74, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-25846134
ABSTRACT
BACKGROUND:
Gastroesophageal reflux can cause high acidity in the esophagus and trigger heartburn and pain. However, because of the esophageal mucosal barrier, the acidity at the nerve terminals of pain-mediating C-fibers in esophageal mucosa is predicted to be substantially lower. We hypothesized that the esophageal dorsal root ganglia (DRG) C-fibers are activated by mild acid (compared to acidic reflux), and express receptors and ion channels highly sensitive to acid.METHODS:
Extracellular single unit recordings of activity originating in esophageal DRG C-fiber nerve terminals were performed in the innervated esophagus preparation ex vivo. Acid was delivered in a manner that bypassed the esophageal mucosal barrier. The expression of mRNA for selected receptors in esophagus-specific DRG neurons was evaluated using single cell RT-PCR. KEYRESULTS:
Mild acid (pH = 6.5-5.5) activated esophageal DRG C-fibers in a pH-dependent manner. The response to mild acid at pH = 6 was not affected by the TRPV1 selective antagonist iodo-resiniferatoxin. The majority (70-95%) of esophageal DRG C-fiber neurons (TRPV1-positive) expressed mRNA for acid sensing ion channels (ASIC1a, ASIC1b, ASIC2b, and/or ASIC3), two-pore-domain (K2P) potassium channel TASK1, and the proton-sensing G-protein coupled receptor OGR1. Other evaluated targets (PKD2L1, TRPV4, TASK3, TALK1, G2A, GPR4, and TDAG8) were expressed rarely. CONCLUSIONS & INFERENCES Guinea pig esophageal DRG C-fibers are activated by mild acid via a TRPV1-independent mechanism, and express mRNA for several receptors and ion channels highly sensitive to acid. The high acid sensitivity of esophageal C-fibers may contribute to heartburn and pain in conditions of reduced mucosal barrier function.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Nociceptores
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ARN Mensajero
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Fibras Nerviosas Amielínicas
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Esófago
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Canales Iónicos Sensibles al Ácido
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Ganglios Espinales
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Ácido Clorhídrico
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Neuronas
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2015
Tipo del documento:
Article