{"title":"丹参素通过增强小鼠耳蜗神经核丛细胞中的钾电流来降低神经元的兴奋性。","authors":"Mengfan Xu, Liqin Wang, Geng-Lin Li, Zheng-Quan Tang","doi":"10.1097/WNR.0000000000002047","DOIUrl":null,"url":null,"abstract":"<p><p>Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system. We prepared brain slices of the mouse brainstem and performed patch-clamp recording in bushy cells in the anteroventral cochlear nucleus, with or without Danshensu incubation for 1 h. QX-314 was used internally to block Na+ current, while tetraethylammonium and 4-aminopyridine were used to isolate different subtypes of K+ current. We found that Danshensu of 100 μm decreased the input resistance of bushy cells by approximately 60% and shifted the voltage threshold of spiking positively by approximately 7 mV, resulting in significantly reduced excitability. Furthermore, we found this reduced excitability by Danshensu was caused by enhanced voltage-gated K+ currents in these neurons, including both low voltage-activated IK,A, by approximately 100%, and high voltage-activated IK,dr, by approximately 30%. Lastly, we found that the effect of Danshensu on K+ currents was dose-dependent in that no enhancement was found for Danshensu of 50 μm and Danshensu of 200 μm failed to cause significantly more enhancement on K+ currents when compared to that of 100 μm. We found that Danshensu reduced neuronal excitability in the central nervous system by enhancing voltage-gated K+ currents, providing mechanistic support for its neuroprotective effect widely seen in vivo.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"35 10","pages":"638-647"},"PeriodicalIF":1.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Danshensu reduces neuronal excitability by enhancing potassium currents in bushy cells in the mouse cochlear nucleus.\",\"authors\":\"Mengfan Xu, Liqin Wang, Geng-Lin Li, Zheng-Quan Tang\",\"doi\":\"10.1097/WNR.0000000000002047\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system. We prepared brain slices of the mouse brainstem and performed patch-clamp recording in bushy cells in the anteroventral cochlear nucleus, with or without Danshensu incubation for 1 h. QX-314 was used internally to block Na+ current, while tetraethylammonium and 4-aminopyridine were used to isolate different subtypes of K+ current. We found that Danshensu of 100 μm decreased the input resistance of bushy cells by approximately 60% and shifted the voltage threshold of spiking positively by approximately 7 mV, resulting in significantly reduced excitability. Furthermore, we found this reduced excitability by Danshensu was caused by enhanced voltage-gated K+ currents in these neurons, including both low voltage-activated IK,A, by approximately 100%, and high voltage-activated IK,dr, by approximately 30%. Lastly, we found that the effect of Danshensu on K+ currents was dose-dependent in that no enhancement was found for Danshensu of 50 μm and Danshensu of 200 μm failed to cause significantly more enhancement on K+ currents when compared to that of 100 μm. We found that Danshensu reduced neuronal excitability in the central nervous system by enhancing voltage-gated K+ currents, providing mechanistic support for its neuroprotective effect widely seen in vivo.</p>\",\"PeriodicalId\":19213,\"journal\":{\"name\":\"Neuroreport\",\"volume\":\"35 10\",\"pages\":\"638-647\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroreport\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/WNR.0000000000002047\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroreport","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/WNR.0000000000002047","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/20 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Danshensu reduces neuronal excitability by enhancing potassium currents in bushy cells in the mouse cochlear nucleus.
Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system. We prepared brain slices of the mouse brainstem and performed patch-clamp recording in bushy cells in the anteroventral cochlear nucleus, with or without Danshensu incubation for 1 h. QX-314 was used internally to block Na+ current, while tetraethylammonium and 4-aminopyridine were used to isolate different subtypes of K+ current. We found that Danshensu of 100 μm decreased the input resistance of bushy cells by approximately 60% and shifted the voltage threshold of spiking positively by approximately 7 mV, resulting in significantly reduced excitability. Furthermore, we found this reduced excitability by Danshensu was caused by enhanced voltage-gated K+ currents in these neurons, including both low voltage-activated IK,A, by approximately 100%, and high voltage-activated IK,dr, by approximately 30%. Lastly, we found that the effect of Danshensu on K+ currents was dose-dependent in that no enhancement was found for Danshensu of 50 μm and Danshensu of 200 μm failed to cause significantly more enhancement on K+ currents when compared to that of 100 μm. We found that Danshensu reduced neuronal excitability in the central nervous system by enhancing voltage-gated K+ currents, providing mechanistic support for its neuroprotective effect widely seen in vivo.
期刊介绍:
NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works.
We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.