Functional involvement of acid-sensing ion channel 3 in the swallowing reflex in rats
Functional involvement of acid-sensing ion channel 3 in the swallowing reflex in rats
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DOI：
10.1111/nmo.13728
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发表时间：
2019-09-29
影响因子：
3.5
通讯作者：
Kitagawa, Junichi
中科院分区：
文献类型：
--
作者：
Hossain, Mohammad Zakir;Ando, Hiroshi;Kitagawa, Junichi
背景吞咽困难是一个主要的健康问题。吞咽功能是通过在悬浮液/食物丸中加入弱酸来改善的，这涉及到吞咽反射中的酸感离子通道(ASIC)。然而，ASICs参与吞咽反射的功能尚未完全阐明。方法将ASIC3定位于大鼠喉上神经支配的吞咽相关区域(SLNS)和结状-岩-颈神经节复合体(NPJc)，观察它们在诱发吞咽反射中的作用。主要结果我们将ASIC3定位于SLN支配的吞咽相关区域的上皮细胞和神经纤维上。在NPJc，大约一半的SLN传入神经元表达ASIC3。三分之二的ASIC3位于结状神经节和岩神经节的无髓神经元上。在颈静脉神经节中，它们平均分布于无髓神经元和有髓神经元。在吞咽相关区域局部应用人工合成的非质子ASIC3激动剂2-胍-4-甲基喹唑啉(GMQ)及其天然内源性配体胍丁胺(氨基酸精氨酸的代谢物)，可引起相当数量的吞咽反射。当GMQ和胍丁胺浓度增加到一定浓度时，诱发反射的数目增加，两次诱发反射的间隔缩短。与GMQ相比，Agmatine唤起吞咽反射的能力较弱。预先局部应用ASIC3拮抗剂可显著减弱GMQ和胍丁胺引起的吞咽反射的数量。结论：推测位于吞咽相关区域神经和上皮细胞上的酸敏离子通道3S具有唤起吞咽反射的功能，并且通过药物激动剂激活这些通道似乎可以改善吞咽行为。
Background Difficulty swallowing represents a major health problem. Swallowing function is improved by incorporating weak acids in suspensions/food boluses, implicating acid-sensing ion channels (ASICs) in the swallowing reflex. However, the functional involvement of ASICs in the swallowing reflex has not been fully elucidated. Methods We localized ASIC3s in swallowing-related regions innervated by the superior laryngeal nerves (SLNs) and those in the nodose-petrosal-jugular ganglionic complex (NPJc) and examined their functional involvement in evoking the swallowing reflex in rats. Key Results We localized ASIC3s on epithelial cells and nerve fibers in swallowing-related regions innervated by the SLNs. In the NPJc, around half of the SLN-afferent neurons expressed ASIC3. Two-thirds of ASIC3s were localized on unmyelinated neurons in the nodose and petrosal ganglia. In the jugular ganglia, they were equally distributed on unmyelinated and myelinated neurons. Topical application of a synthetic non-proton ASIC3 activator, 2-guanidine-4-methylquinazoline (GMQ), and its natural endogenous ligand agmatine (a metabolite of the amino acid arginine) in swallowing-related regions evoked a considerable number of swallowing reflexes. Increasing the concentration of GMQ and agmatine up to a certain concentration increased the number of evoked reflexes and shortened the interval between the evoked reflexes. Agmatine was less potent than GMQ in its ability to evoke swallowing reflexes. Prior topical application of an ASIC3 antagonist significantly attenuated the number of GMQ- and agmatine-evoked swallowing reflexes. Conclusions & Inferences Acid-sensing ion channel 3s localized on nerves and epithelial cells in swallowing-related regions are functional in evoking the swallowing reflex and activation of these channels via a pharmacological agonist appears to improve swallowing behavior.