Neurophysiological and molecular approach for evaluating mechanism of pathogenesis of febrile seizure

评估热性惊厥发病机制的神经生理学和分子方法

• 批准号: 14370241
• 负责人: IINUMA Kazuie
• 金额: $ 7.1万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370241/
• 关键词: Febrile seizure; sodium channel; potassium channel; voltage-gated; abnormal channel; temperature change; antihistaminic agents; patch clamp; NA+チャネル; Na^+チャネル; K^+チャネル; チャネル以上

Recently gene abnormality which codes alpha or beta subunit of the sodium channel such as SCN1A was revealed in a case with febrile seizures. The purpose of this study is to evaluate the effect of increased temperature to the sodium channel by method of patch clamp. In our previous research, we disclosed that the incidence of seizures was significantly increased in cases of children with fever when they were given antihistaminic agents. We evaluated the effect of first-generation antihistaminic agents to 2 potassium channels. The antihistaminics suppressed potassium channels, especially to M-current. We suggested that the standard antihistaminic agent, pyrilamine acted directly on the M-channel pores. H2-receptor antagonists did not affect the M-channel. The inhibition of M channels may be involved in the neurotoxic effects of first-generation antihistaminics overdose.In ordinary patch clamp experiments, the temperature of fluid in the chamber is kept about 25℃, but we tried to make the environmental temperature higher. However, the ordinary Y-tube did not make steady temperature. Then we created loop shaped Y-tube which successfully kept the temperature of the medium about 35℃. Eventually we could record sodium channel current at 40℃.

最近在一例热性惊厥中发现了编码钠通道α或β亚基的基因异常，如SCN1A。本研究的目的是用膜片钳法评估温度升高对钠通道的影响。在我们之前的研究中，我们披露了在给予抗组胺药的情况下，发烧儿童癫痫发作的发生率显着增加。我们评估了第一代抗组胺药对2个钾通道的影响。抗组胺药抑制钾通道，特别是对m电流。我们建议标准抗组胺剂吡咯胺直接作用于m通道孔。h2受体拮抗剂不影响m通道。第一代抗组胺药过量的神经毒性作用可能与M通道的抑制有关。在普通膜片钳实验中，腔内流体温度保持在25℃左右，但我们试图使环境温度更高。然而，普通的y形管不能产生稳定的温度。然后我们制作了环形y形管，成功地将介质温度保持在35℃左右。最终我们可以在40℃下记录钠离子通道电流。