Studies of voltage sensor and ion permeability in HCN channels

• Project/Area Number: 19590208
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Kyoto University
• Principal Investigator: ISHII Takahiro Kyoto University, 医学研究科, 准教授 (40303812)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 分子生理学 / 過分極 / イオンチャネル / Ih / HCN / 電位センサー / 多量体 / ゲート機構 / 点変異 / チャネル / システイン残基 / ジスルフィド結合

Research Abstract

通常の電位依存性イオンチャネルは脱分極で活性化するのに対し、過分極で活性化するという特異な性質をもつHCNチャネルの活性化速度を決定する部位の検索と電位を感じる部位の構造解析を行った. その結果、活性化速度には第一膜貫通領域が重要で、電位を感じる部位を構成する第一膜貫通領域と第四膜貫通領域の相対位置が明らかとなった. これらの結果は、HCNチャネルの開閉メカニズムを理解する上で重要で、生理学的役割を理解する上で重要な知見を与える.

Research Products

• [Journal Article] HCN and Cav3 ion Channels Confer Automaticity of Embryonic Stem Cell-derived Cardiomyocytes" (2007)
  • Author(s): Kentoku Yanagi, Makoto Takano, Genta Narazaki, Hideki Uosaki, Takuhiro Hoshino, Takahiro Ishii, Takurou Misaki, and Jun K Yamashita
  • Journal Title: Stem Cells 25 Pages: 2712-9
  • Peer Reviewed
• [Journal Article] Peripheral Nand C-terminal domains determine deactivation kinetics of HCN channels (2007)
  • Author(s): Takahiro M. Ishii, Noriyuki Nakashima, Kenji Takatsuka, and Harunori Ohmori
  • Journal Title: Biochem. Biophys. Res. Comm 359 Pages: 592-598
  • Peer Reviewed
• [Journal Article] Mechanistic basis for the pathogenesis of long QT syndrome associated with a common splicing mutation in KCNQ1 gene (2007)
  • Author(s): Keiko Tsuji, Masaharu Akao, Takahiro M. Ishii, Seiko Ohno, Takeru Makiyama, Kotoe Takenaka, Takahiro Doi, Yoshisumi Haruna, Hidetada Yoshida, Toshihiro Nakashima, Toru Kita, and Minoru Horie
  • Journal Title: Journal of Molecular and Cellular Cardiology 42 Pages: 662-669
  • Peer Reviewed
• [Journal Article] Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice (2007)
  • Author(s): Haruhiko Akiyama, H. Scott Stadler, James F. Martin, Takahiro M. Ishii, Philip A. Beachy, Takashi Nakamura, and Benoit de Crombruggh
  • Journal Title: Matrix Biology 26 Pages: 224-33
  • Peer Reviewed
• [Journal Article] Tryptophan scanning mutagenesis in the S1 domain of mammalian HCN channel reveals residues critical for voltage-gated activation (2007)
  • Author(s): Takahiro M. Ishii, Noriyuki Nakashima, and Harunori Ohmori
  • Journal Title: J. Physiology 579.2 Pages: 291-301
  • Peer Reviewed
• [Journal Article] NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes (2007)
  • Author(s): Shinobu Kuratomi, Akiko Kuratomi, Koichiro Kuwahara, Takahiro M. Ishii, Kazuwa Nakao, Yoshihiko Saito, and Makoto Takano
  • Journal Title: Biochem. Biophys. Res. Comm 353 Pages: 67-73
  • Peer Reviewed
• [Journal Article] HCN and Cav3 ion Channels Confer Automaticity of Embryonic Stem Cell-derived Cardiomyocytes (2007)
  • Author(s): Kentoku Yanagi, Makoto Takano, Genta Narazaki, Hideki Uosakii, Takuhiro Hoshino, Takabiro Ishii, Takurou Misaki, and Jun K. Yamashita
  • Journal Title: Stem Cells 25 Pages: 2712-2719
  • Peer Reviewed
• [Journal Article] Peripheral N-and C-terminal domains determine deactivation kinetics of HCN channels (2007)
  • Author(s): Takahiro M. Ishii, Noriyuki Nakashima, Kenji Takatsuka, and Harunori Ohmori
  • Journal Title: Biochem. Biophys. Res. Comm. 359 Pages: 592-598
  • Peer Reviewed
• [Journal Article] Mechanistic basis for the pathogenesis of long QT syndrome associated with a common splicing mutation in KCNQ1 gene (2007)
  • Author(s): Keiko Tsuji, Masaharu Akao, Takahiro M. Ishii, Seiko Ohno, Takeru Makiyama, Kotoe Takenaka, Takahiro Doi, Yoshisumi Haruna, Hidetada Yoshida, Toshihiro Nakashima, Toru Kita, and Minoru Horie
  • Journal Title: Journal of Molecular and Cellular Cardiolog 42 Pages: 662-669
  • Peer Reviewed
• [Journal Article] Tryptophan scanning mutagenesis in the S1 domain of mammalian HCN channel reveals residues critical for voltage-gated activation (2007)
  • Author(s): Takahiro M. Ishii, Noriyuki Nakashima, and Harunori Ohmori
  • Journal Title: J. Physiology 579 Pages: 291-301
  • Peer Reviewed
• [Journal Article] NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes (2007)
  • Author(s): Shinobu Kuratomi, Akiko Kuratomi, Koichiro Kuwahara, Takahiro M. Ishii, Kazuwa Nakao, Yoshihiko Saito, and Makoto Takano
  • Journal Title: Biochem. Biophys. Res. Comm. 353 Pages: 67-63
  • Peer Reviewed
• [Presentation] HCNチャネルの電位センサー領域の構造と機能に関する研究 (2008)
  • Author(s): 石井孝広, 中島則行, 大森治紀
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] HCNチャネルにおける電位センサーの機能と構造の関係 (2008)
  • Author(s): 石井孝広、中島則行、大森治紀
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-25
• [Presentation] Structure-function relationship of voltage sensor in HCN channels (2008)
  • Author(s): Takahiro Ishii, Noriyuki Nakashima, and Harunori Ohmori
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] HCNチャネルの電位センサー領域の構造と機能に関する研究 (2008)
  • Author(s): 石井孝広、中島則行、大森治紀
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://www.nbiol.med.kyoto-u.ac.jp
• [Remarks]
  • URL: http://www.nbiol.med.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://www.nbiol.med.kyoto-u.ac.jp