Role of voltage-gated chloride channels in epilepsy: current insights and future directions
Epilepsy is a prevalent chronic neurological disorder characterised by recurrent seizures caused by excessive neuronal discharge. Disruptions in chloride ion homeostasis significantly affect neuronal excitability, and play a crucial role in the pathophysiology of this disorder. This review highlight...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1560392/full |
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| author | Ming-Ming Ni Jie-Yu Sun Zheng-Qian Li Jin-Chun Qiu Chun-Feng Wu |
| author_facet | Ming-Ming Ni Jie-Yu Sun Zheng-Qian Li Jin-Chun Qiu Chun-Feng Wu |
| author_sort | Ming-Ming Ni |
| collection | DOAJ |
| description | Epilepsy is a prevalent chronic neurological disorder characterised by recurrent seizures caused by excessive neuronal discharge. Disruptions in chloride ion homeostasis significantly affect neuronal excitability, and play a crucial role in the pathophysiology of this disorder. This review highlights the emerging importance of chloride voltage-gated channels in epilepsy, which has been largely underappreciated compared to cation channels. Recent studies have suggested that genetic alterations in chloride channels, such as CLCN1, CLCN2, CLCN3, CLCN4, and CLCN6, contribute to neuronal excitability and seizure susceptibility, with variations in these channels acting more as susceptibility factors than direct causes. However, there is a significant gap in the research on other chloride channels, particularly ClC-Ka, ClC-Kb, ClC-5, and ClC-7, whose roles in epilepsy remain underexplored. Future research should focus on these channels to better understand their contribution to the pathophysiology of epilepsy. The incorporation of genetic tests for chloride channel variants in clinical practice could provide valuable insight into the aetiology of epilepsy, leading to improved diagnostic and therapeutic strategies for affected individuals. |
| format | Article |
| id | doaj-art-d10c9dfeee834f90bef58f728d2e9b8c |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-d10c9dfeee834f90bef58f728d2e9b8c2025-08-20T02:48:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15603921560392Role of voltage-gated chloride channels in epilepsy: current insights and future directionsMing-Ming Ni0Jie-Yu Sun1Zheng-Qian Li2Jin-Chun Qiu3Chun-Feng Wu4Department of Pharmacy, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacy, Qinghai Maternal and Child Health Hospital, Xining, ChinaDepartment of Pharmacy, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaEpilepsy is a prevalent chronic neurological disorder characterised by recurrent seizures caused by excessive neuronal discharge. Disruptions in chloride ion homeostasis significantly affect neuronal excitability, and play a crucial role in the pathophysiology of this disorder. This review highlights the emerging importance of chloride voltage-gated channels in epilepsy, which has been largely underappreciated compared to cation channels. Recent studies have suggested that genetic alterations in chloride channels, such as CLCN1, CLCN2, CLCN3, CLCN4, and CLCN6, contribute to neuronal excitability and seizure susceptibility, with variations in these channels acting more as susceptibility factors than direct causes. However, there is a significant gap in the research on other chloride channels, particularly ClC-Ka, ClC-Kb, ClC-5, and ClC-7, whose roles in epilepsy remain underexplored. Future research should focus on these channels to better understand their contribution to the pathophysiology of epilepsy. The incorporation of genetic tests for chloride channel variants in clinical practice could provide valuable insight into the aetiology of epilepsy, leading to improved diagnostic and therapeutic strategies for affected individuals.https://www.frontiersin.org/articles/10.3389/fphar.2025.1560392/fullchloride channelsepilepsyion channelsneuronal excitabilitygenetic variants |
| spellingShingle | Ming-Ming Ni Jie-Yu Sun Zheng-Qian Li Jin-Chun Qiu Chun-Feng Wu Role of voltage-gated chloride channels in epilepsy: current insights and future directions Frontiers in Pharmacology chloride channels epilepsy ion channels neuronal excitability genetic variants |
| title | Role of voltage-gated chloride channels in epilepsy: current insights and future directions |
| title_full | Role of voltage-gated chloride channels in epilepsy: current insights and future directions |
| title_fullStr | Role of voltage-gated chloride channels in epilepsy: current insights and future directions |
| title_full_unstemmed | Role of voltage-gated chloride channels in epilepsy: current insights and future directions |
| title_short | Role of voltage-gated chloride channels in epilepsy: current insights and future directions |
| title_sort | role of voltage gated chloride channels in epilepsy current insights and future directions |
| topic | chloride channels epilepsy ion channels neuronal excitability genetic variants |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1560392/full |
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