2004 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number	14370241
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Pediatrics
Research Institution	TOHOKU UNIVERSITY
Principal Investigator	IINUMA Kazuie Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80004927)
Co-Investigator(Kenkyū-buntansha)	HAGINOYA Kazuhiro Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (00208414) YOKOYAMA Hiroyuki Tohoku University, Hospital, Research Associate, 病院・助手 (40271952) KURE Shigeo Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10205221)
Project Period (FY)	2002 – 2004
Keywords	Febrile seizure / sodium channel / potassium channel / voltage-gated / abnormal channel / temperature change / antihistaminic agents / patch clamp
Research Abstract	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℃.