Changes in the expression of HCN ion channels leading to changes in I_h function and neuronal excitability are considered to be possible mechanisms involved in epileptogenesis in kinds of human epilepsy. In previous animal studies of febrile seizures and temporal lobe epilepsy, changes in the expression of HCN1 and HCN2 channels at different time points and in different parts of the brain were not consistent, suggesting that transcriptional disorders involving HCNs play a crucial role in the epileptogenic process. Therefore, we aimed to assess the transcriptional regulation of HCN channels in Medial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) patients. This study included eight nonhippocampal sclerosis patients and 40 MTLE‐HS patients. The mRNA expression of HCN channels was evaluated by qRT‐PCR, while the protein expression was quantitatively analyzed by Western blotting. The subcellular localization of HCN channels in the hippocampus was explored by immunofluorescence. We demonstrated that the mRNA and protein expression of HCN1 and HCN2 are downregulated in controls compared to that in MTLE‐HS patients. In the hippocampal CA1/CA4 subregion and GCL, in addition to a large decrease in neurons, the expression of HCN1 and HCN2 on neuronal cell membranes was also downregulated in MTLE‐HS patients. These findings suggest that the expression of HCN channels are downregulated in MTLE‐HS, which indicates that the decline in HCN channels in the hippocampus during chronic epilepsy in MTLE‐HS patients leads to the downregulation of I_h current density and function, thereby reducing the inhibitory effect and increasing neuronal excitability and eventually causing disturbances in the electrical activity of neurons.

中文翻译：

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内侧颞叶癫痫和海马硬化 (MTLE-HS) 患者海马中超极化激活的环核苷酸门控通道 (HCN) 的下调。

HCN离子通道表达的变化导致I _h的变化功能和神经元兴奋性被认为是参与各种人类癫痫的癫痫发生的可能机制。在之前对热性惊厥和颞叶癫痫的动物研究中，HCN1 和 HCN2 通道在不同时间点和大脑不同部位的表达变化并不一致，表明涉及 HCN 的转录障碍在癫痫发生过程中起着至关重要的作用. 因此，我们旨在评估内侧颞叶癫痫伴海马硬化 (MTLE-HS) 患者中 HCN 通道的转录调控。该研究包括 8 名非海马硬化患者和 40 名 MTLE-HS 患者。通过 qRT-PCR 评估 HCN 通道的 mRNA 表达，而通过蛋白质印迹定量分析蛋白质表达。通过免疫荧光探索了海马中 HCN 通道的亚细胞定位。我们证明，与 MTLE-HS 患者相比，HCN1 和 HCN2 的 mRNA 和蛋白质表达在对照组中下调。在海马CA1/CA4亚区和GCL中，除了神经元大量减少外，MTLE-HS患者神经元细胞膜上HCN1和HCN2的表达也下调。这些发现表明 MTLE-HS 中 HCN 通道的表达下调，这表明 MTLE-HS 患者慢性癫痫期间海马中 HCN 通道的下降导致 我们证明，与 MTLE-HS 患者相比，HCN1 和 HCN2 的 mRNA 和蛋白质表达在对照组中下调。在海马CA1/CA4亚区和GCL中，除了神经元大量减少外，MTLE-HS患者神经元细胞膜上HCN1和HCN2的表达也下调。这些发现表明 MTLE-HS 中 HCN 通道的表达下调，这表明 MTLE-HS 患者慢性癫痫期间海马中 HCN 通道的下降导致 我们证明，与 MTLE-HS 患者相比，HCN1 和 HCN2 的 mRNA 和蛋白质表达在对照组中下调。在海马CA1/CA4亚区和GCL中，除了神经元大量减少外，MTLE-HS患者神经元细胞膜上HCN1和HCN2的表达也下调。这些发现表明 MTLE-HS 中 HCN 通道的表达下调，这表明 MTLE-HS 患者慢性癫痫期间海马中 HCN 通道的下降导致I _h电流密度和功能，从而降低抑制作用并增加神经元兴奋性，最终导致神经元电活动紊乱。