Action potential-dependent α4-containing GABAA receptors contribute to epileptogenicity in focal cortical dysplasia

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2025-02-01 DOI:10.1016/j.eplepsyres.2025.107520

Yogesh Aggarwal , Aparna Banerjee Dixit , Manjari Tripathi , Ramesh Doddamani , Meher Chand Sharma , P.Sarat Chandra , Jyotirmoy Banerjee

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Abstract

FCD is a developmental disorder associated with drug-resistant seizures. Alterations in GABA_A receptor-mediated activity contribute to seizures in FCD. However, the exact mechanism of altered GABAergic synaptic activity is still unclear. Previously, we showed increased GABA_A receptor α4 subunit expression in FCD. In this study, we investigated whether changes in GABA_A receptor configuration at synaptic or extrasynaptic sites contribute to enhanced GABAergic activity in the resected samples of FCD patients. Results showed increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents on treatment with gaboxadol (agonist for α4δ-containing GABA_A receptors). In the presence of tetrodotoxin (voltage-gated Na⁺ channel inhibitor), frequency and amplitude of miniature inhibitory postsynaptic currents were also increased upon treatment with gaboxadol. However, higher magnitude of change was observed in spontaneous inhibitory postsynaptic currents compared to miniature inhibitory postsynaptic currents on gaboxadol treatment, suggesting action potential-dependent α4-containing GABA_A receptor activity may influence epileptogenicity in FCD.

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动作电位依赖性α4-含GABAA受体参与局灶性皮质发育不良的致痫性

FCD是一种与耐药癫痫发作相关的发育障碍。GABAA受体介导的活性改变有助于FCD患者癫痫发作。然而，gaba能突触活性改变的确切机制尚不清楚。先前，我们发现GABAA受体α4亚基在FCD中的表达增加。在这项研究中，我们研究了突触或突触外GABAA受体结构的变化是否有助于FCD患者切除样本中GABAA能活性的增强。结果表明，加博沙多（含α4δ- GABAA受体的激动剂）可增加自发性抑制性突触后电流的频率和幅度。在河豚毒素（电压门控Na+通道抑制剂）存在的情况下，加博沙多也增加了微型抑制性突触后电流的频率和幅度。然而，与加博沙多治疗的微抑制性突触后电流相比，自发性抑制性突触后电流的变化幅度更大，这表明动作电位依赖性α4- GABAA受体活性可能影响FCD的致痫性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.