Functional analysis using iPS cells for novel HCN2 mutation found in febrile seizure patients.

• Project/Area Number: 24791096
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Fukuoka University
• Principal Investigator: NAKAMURA Yuki 福岡大学, 医学部, 助手 (90535072)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: イオンチャネル / パッチクランプ / 電気生理 / 熱性けいれん / 遺伝子変異 / 過分極活性型環状ヌクレオチド依存性チャネル / iPS細胞 / 小児科 / 変異 / 遺伝子 / 神経科学 / 小児科学

Outline of Final Research Achievements

Novel HCN2 mutation (S126L) found in Febrile Seizure patients was transfected to iPS cells and cultured neurons. The function of HCN mutant protein was examined by using the patch clamp method. The conductance in rat CA1 neurons transfected mutant HCN2 was increased and the distribution of the channel protein showed migration to the cell membrane in PC12 cells. These results of the neuronal cells' experiment was similar to that of the cultured cells' experiment.
These results suggest that animals with this HCN2 mutation might have the possibility of causing Febrile Seizure. And these results might help to elucidate the mechanism of Febrile Seizure.

Research Products

• [Journal Article] Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner (2013)
  • Author(s): Yuki Nakamura, Xiuyu Shi, Tomohiro Numata, Yasuo Mori, Ryuji Inoue, Christoph Lossin, Tallie Z. Baram, Shinichi Hirose
  • Journal Title: PLoS One Volume: 8(12) Issue: 12 Pages: e80376-e80376
  • DOI: 10.1371/journal.pone.0080376
  • Peer Reviewed
• [Journal Article] てんかんの分子病態 (2012)
  • Author(s): 井原由紀子 石井敦士 日暮憲道 内田琢 中村友紀 友納優子 廣瀬伸一
  • Journal Title: Medical Science Digest Volume: 38 Pages: 292-295
• [Journal Article] てんかんと遺伝子 (2012)
  • Author(s): 廣瀬伸一 日暮憲道 中村友紀 黄壽卿 石井敦士
  • Journal Title: Modern Physician Volume: 32 Pages: 282-288
• [Journal Article] てんかんにおけるGABA受容体とK+チャネルの異常 (2012)
  • Author(s): 石井敦士 内田琢 中村友紀 廣瀬伸一
  • Journal Title: Clinical Neuroscience Volume: 30 Pages: 1397-1400
• [Presentation] The identification and characterization of novel HCN2 mutation found in febrile seizure patients (2015)
  • Author(s): Yuki Nakamura
  • Organizer: 25th meeting of the International Society for Neurochemistry
  • Place of Presentation: Cairns Convention Centre, Australia
  • Year and Date: 2015-08-23 – 2015-08-27
  • Invited
• [Presentation] Novel HCN2 mutation found in febrile seizure patients shifts the temperature sensitivity. (2014)
  • Author(s): Yuki Nakamura
  • Organizer: The 45th NIPS Internaional Symposium, co-sponsored by The Journal of Physiology
  • Place of Presentation: 生理学研究所
  • Year and Date: 2014-11-25 – 2014-11-28
• [Presentation] 家族性熱性けいれんにて発見されたHCNチャネル遺伝子変異の機能解析
  • Author(s): 中村友紀
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学
• [Presentation] Novel HCN2 mutation causing febrile seizure shifts the activation voltage in a temperature dependent manner.
  • Author(s): Yuki Nakamura
  • Organizer: The 11th Korea-Japan Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscle Sciences
  • Place of Presentation: Act City Hamamatsu Congress Center
• [Presentation] Electrophysiological analysis of mutant HCN channels found in febrile seizure patients
  • Author(s): Yuki Nakamura
  • Organizer: Korean Epilepsy Congress 2013
  • Place of Presentation: Grand Hilton Hotel, Korea
• [Presentation] Effects of hyperthermia on novel HCN2 mutant channels found in febrile seizure patients
  • Author(s): Nakamura Yuki
  • Organizer: Joint Congress of the 12th International Child Neurology Congress and the 11th Asian and Oceanian Congress of Child Neurology
  • Place of Presentation: Brisbane Convention & Exhibition Center, Australia
• [Presentation] Novel HCN2 mutation causing febrile seizure shifts the activation voltage in a temperature dependent manner.
  • Author(s): Nakamura Yuki
  • Organizer: The 2nd International Symposium of Central Research Institute for the Molecular Pathomechanisms of Epilepsy
  • Place of Presentation: 福岡大学
• [Presentation] 熱性けいれん患者において発見されたHCN2変異遺伝子の生理的温度付近における機能解析
  • Author(s): 中村友紀
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀
• [Remarks] 福岡大学 てんかん分子病態研究所
  • URL: http://www.med.fukuoka-u.ac.jp/epilepsy/index.html