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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 TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTOHOKU 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)
宗形 光敏  東北大学, 医学部附属病院, 助手 (30312573)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsFebrile 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
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℃.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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