The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes
The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes
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DOI：
10.1152/ajpgi.00129.2014
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发表时间：
2014-11-01
影响因子：
4.5
通讯作者：
Kollarik, Marian
中科院分区：
文献类型：
--
作者：
Dusenkova, Svetlana;Ru, Fei;Kollarik, Marian
酸敏感离子通道（ASIC）与食管酸敏感和机械转导有关。然而，对食管传入神经中ASIC亚基表达谱的认识不足阻碍了对其作用的理解。这些知识至关重要，因为ASIC亚基形成具有不同功能特性的异多聚体通道。我们假设，食管假定的伤害性C纤维神经（瞬时受体电位香草酸1，TRPV 1阳性）表达多个ASIC亚基和ASIC的表达谱之间的结节TRPV 1阳性亚型发育来自基板和颈静脉TRPV 1阳性亚型来自神经嵴不同。我们进行了单细胞RT-PCR的迷走神经传入神经元逆行标记的食管。在豚鼠中，几乎所有（90%-95%）结状和颈静脉食管TRPV 1阳性神经元表达ASIC，最常见的是组合（65-75%）。ASIC 1、ASIC 2和ASIC 3分别在结状和颈静脉TRPV 1阳性神经元中表达65- 75%、55- 70%和70%。ASIC 1剪接变体ASIC 1a和ASIC 1b以及ASIC 2剪接变体ASIC 2b在结状核和颈静脉TRPV 1阳性神经元中表达相似。然而，ASIC 2a被发现只在结状神经元。与豚鼠相反，小鼠迷走神经食管TRPV 1阳性神经元中几乎不存在ASIC 3。然而，ASIC 3在两个物种的非伤害性TRPV 1阴性（张力机械感受器）神经元中表达相似。我们的结论是，大多数食管迷走神经伤害性神经元表达多种ASIC亚单位。基板衍生的结状核神经元选择性地表达ASIC 2a，已知其显著降低ASIC异多聚体的酸敏感性。ASIC 3在豚鼠中表达，但在小鼠迷走神经食管TRPV 1阳性神经元中不表达，表明ASIC表达的种属差异。
Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties. We hypothesized that the esophageal putative nociceptive C-fiber nerves (transient receptor potential vanilloid 1, TRPV1-positive) express multiple ASIC subunits and that the ASIC expression profile differs between the nodose TRPV1-positive subtype developmentally derived from placodes and the jugular TRPV1-positive subtype derived from neural crest. We performed single cell RT-PCR on the vagal afferent neurons retrogradely labeled from the esophagus. In the guinea pig, nearly all (90%-95%) nodose and jugular esophageal TRPV1-positive neurons expressed ASICs, most often in a combination (65-75%). ASIC1, ASIC2, and ASIC3 were expressed in 65-75%, 55-70%, and 70%, respectively, of both nodose and jugular TRPV1-positive neurons. The ASIC1 splice variants ASIC1a and ASIC1b and the ASIC2 splice variant ASIC2b were similarly expressed in both nodose and jugular TRPV1-positive neurons. However, ASIC2a was found exclusively in the nodose neurons. In contrast to guinea pig, ASIC3 was almost absent from the mouse vagal esophageal TRPV1-positive neurons. However, ASIC3 was similarly expressed in the nonnociceptive TRPV1-negative (tension mechanoreceptors) neurons in both species. We conclude that the majority of esophageal vagal nociceptive neurons express multiple ASIC subunits. The placode-derived nodose neurons selectively express ASIC2a, known to substantially reduce acid sensitivity of ASIC heteromultimers. ASIC3 is expressed in the guinea pig but not in the mouse vagal esophageal TRPV1-positive neurons, indicating species differences in ASIC expression.