Ru F, Banovcin P, Kollarik M
Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pathophysiology and Gastroenterology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia.
Neurogastroenterol Motil. 2015 Jun;27(6):865-74. doi: 10.1111/nmo.12561. Epub 2015 Apr 5.
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.
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.
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.
胃食管反流可导致食管内酸度升高，引发烧心和疼痛。然而，由于食管黏膜屏障的存在，预计食管黏膜中疼痛介导的C纤维神经末梢处的酸度会显著降低。我们推测食管背根神经节（DRG）C纤维会被弱酸（与酸性反流相比）激活，并表达对酸高度敏感的受体和离子通道。
在离体的受支配食管标本中，对源自食管DRG C纤维神经末梢的活动进行细胞外单单位记录。以绕过食管黏膜屏障的方式给予酸。使用单细胞逆转录聚合酶链反应（RT-PCR）评估食管特异性DRG神经元中选定受体的mRNA表达。
弱酸（pH = 6.5 - 5.5）以pH依赖的方式激活食管DRG C纤维。pH = 6时对弱酸的反应不受TRPV1选择性拮抗剂碘树脂毒素的影响。大多数（70 - 95%）食管DRG C纤维神经元（TRPV1阳性）表达酸敏感离子通道（ASIC1a、ASIC1b、ASIC2b和/或ASIC3）、两孔结构域（K2P）钾通道TASK1以及质子敏感G蛋白偶联受体OGR1的mRNA。其他评估的靶点（PKD2L1、TRPV4、TASK3、TALK1、G2A、GPR4和TDAG8）很少表达。
豚鼠食管DRG C纤维通过不依赖TRPV1的机制被弱酸激活，并表达对酸高度敏感的几种受体和离子通道的mRNA。食管C纤维的高酸敏感性可能在黏膜屏障功能降低的情况下导致烧心和疼痛。
