Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors innervating the guinea pig esophagus.

Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors innervating the guinea pig esophagus.
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DOI:
10.1111/nmo.12561
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发表时间:
2015-06
影响因子:
3.5
通讯作者:
Kollarik M
Kollarik M
中科院分区:
医学3区
文献类型:
--
作者:
Ru F;Banovcin P Jr;Kollarik M

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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 DRG C-fibers are activated by mild acid (compared to acidic reflux), and express receptors and ion channels highly sensitive to acid. 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. 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. 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.
DOI: 10.1152/ajpgi.00129.2014
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