Functional analysis and pharmacological testing of iPSc-derived cardiomyocyte as model for cardiac arrhythmia

• Project/Area Number: 24790745
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: University of Toyama
• Principal Investigator: KINOSHITA Koshi 富山大学, 医学薬学研究部(医学), 助教 (10585920)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 不整脈 / iPS細胞 / QT延長 / 心筋誘導 / 薬剤応答性 / 疾患モデル / 遺伝性心疾患 / LQT / イオンチャネル / パッチクランプ

Research Abstract

We succeeded in inducing cardiomyocyte from iPS cells using only two chemicals, CHIR99021 and IWP-4. Beating was detected within ten days, similar to the conventional method using Activin A and BMP4 proteins. RT-PCR and immunostaining revealed that the induced cardiomyocyte expressed cardiomyocyte-specific genes or proteins. The alterations of beat rate and field potential duration in response to the adrenergic agonist were comparable between the cardiomyocyte derived from a patient carrying a mutation in KCNQ1 gene and healthy control. Using iPS cell-derived cardiomyocyte, various pharmacological testing will become available in the future.

Research Products

• [Journal Article] A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction. (2014)
  • Author(s): Kinoshita K, Komatsu T, Nishide K, Hata Y, Hisajima N, Takahashi H, Kimoto K, Aonuma K, Tushima E, Tabata T, Yoshida T, Mori H, Nishida K, Yamaguchi Y, Ichida F, Fukurotani K, Inoue H, Nishida N.
  • Journal Title: J Mol Cell Cardiol Volume: 72 Pages: 273-280
  • DOI: 10.1016/j.yjmcc.2014.03.019
  • Peer Reviewed / Open Access
• [Journal Article] Identification and characterization of a novel genetic mutation with prolonged QT syndrome in an unexplained postoperative death (2014)
  • Author(s): Yukiko Hata, Hisashi Mori, Ayumi Tanaka, Yosuke Fujita, Takeshi Shimomura, Toshihide Tabata, Koshi Kinoshita, Yoshiaki Yamaguchi, Fukiko Ichida, Yoshihiko Kominato, Noriaki Ikeda, Naoki Nishida
  • Journal Title: International Journal of Legal Medicine Volume: 128 Issue: 1 Pages: 105-115
  • DOI: 10.1007/s00414-013-0853-4
  • Peer Reviewed
• [Journal Article] Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit’s Modulatory Actions on Rapid and Slow Delayed Rectifier K⁺ Currents (2014)
  • Author(s): Yoshiaki Yamaguchi, Kohki Nishide, Mario Kato, Yukiko Hata, Koichi Mizumaki, Koshi Kinoshita, Yuki Nonobe, Toshihide Tabata, Tamotsu Sakamoto, Naoya Kataoka, Yosuke Nakatani, Fukiko Ichida, Hisashi Mori, Kenkichi Fukurotani, Hiroshi Inoue, MD, Naoki Nishida
  • Journal Title: Circulation Journal Volume: 78 Issue: 3 Pages: 610-618
  • DOI: 10.1253/circj.CJ-13-1126
  • NAID: 130003391006
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Characterization of a novel mutant KCNQ1 channel subunit lacking a large part of the C-terminal domain (2013)
  • Author(s): Katsuya Kimoto, Koshi Kinoshita, Tomoki Yokoyama, Yukiko Hata, Takuto Komatsu, Eikichi Tsushima, Kohki Nishide, Yoshiaki Yamaguchi, Koichi Mizumaki, Toshihide Tabata, Hiroshi Inoue, Naoki Nishida, Kenkichi Fukurotani
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 440 Issue: 2 Pages: 283-288
  • DOI: 10.1016/j.bbrc.2013.09.075
  • Peer Reviewed
• [Journal Article] A novel missense mutation causing a G487R substitution in the S2-S3 loop of human ether-a-go-go-related gene channel (2012)
  • Author(s): Kinoshita K, Yamaguchi Y, Nishide K, Kimoto K, Nonobe Y, Fujita A, Asano K, Tabata T, Mori H, Inoue H, Hata Y, Fukurotani K, Nishida N
  • Journal Title: J Cardiovasc Electrophysiol Volume: 23 Issue: 11 Pages: 1246-1253
  • DOI: 10.1111/j.1540-8167.2012.02383.x
  • Peer Reviewed
• [Presentation] C-terminal helix D of KCNQ1 contributes to normal IKs channelfunction. (2014)
  • Author(s): Takuto Komatsu, Koshi Kinoshita, Katsuya Kimoto, Yukiko Hata, Kei Aonuma, Eikichi Tsushima, Kohki Nishide, Nozomi Hisajima, Hiroyuki Takahashi, Kenkichi Fukurotani, Naoki Nishida, Toshihide Tabata
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-03-17
• [Presentation] KCNQ1C末端のhelix Dは正常なIKsチャネル機能に寄与する (2014)
  • Author(s): 小松 卓人、木下 耕史、木本 克哉、畑 由紀子、青沼 慶、津島 永吉、西出 康貴、 久嶋 希望、高橋 宏幸、袋谷 賢吉、西田 尚樹、田端 俊英
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学郡元キャンパス
• [Presentation] Functional Characterization of KCNQ1 Channel Subunit with an A590T mutation. (2013)
  • Author(s): Koshi Kinoshita, Takuto Komatsu, Katsuya Kimoto, Kohki Nishide, Toshihide Tabata, Fukiko Ichida, Yoshiaki Yamaguchi, Kunihiro Nishida, Hiroshi Inoue, Yukiko Hata, Naoki Nishida
  • Organizer: Basic Cardiovascular Sciences (BCVS)
  • Place of Presentation: Las Vegas
  • Year and Date: 2013-07-22
• [Presentation] Abnormal modulation of hERG and KCNQ1 channels. (2013)
  • Author(s): Kohki Nishide, Mario Kato, Yoshiaki Yamaguchi, Koshi Kinoshita, Akira Fujita, Yuki Nonobe, Yukiko Hata, Koichi Mizumaki, Hiroshi Inoue, Naoki Nishida, Toshihide Tabata
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] Characterization of a New Mutant KCNQ1 Channel Subunit with aC-TerminalTruncation. (2013)
  • Author(s): Katsuya Kimoto, Kohki Nishide, Koshi Kinoshita, Yuki Nonobe, Akira Fujita, Yoshiaki Yamaguchi, Yukiko Hata, Koichi Mizumaki, Hiroshi Inoue, Naoki Nishida, Toshihide Tabata
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] Characterization of KCNQ1 (Kv7.1, IKs) channel subunit with an A590Tmutation. (2013)
  • Author(s): Koshi Kinoshita, Toshihide Tabata, Fukiko Ichida, Yoshiaki Yamaguchi, Kunihiro Nishida, Hiroshi Inoue, Yukiko Hata, Naoki Nishida
  • Organizer: 第77回日本循環器学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-15
• [Presentation] Functional Characterization of KCNQ1 Channel Subunit with an A590T Mutation. (2013)
  • Author(s): Koshi Kinoshita, Takuto Komatsu, Katsuya Kimoto, Kohki Nishide, Toshihide Tabata, Fukiko Ichida, Yoshiaki Yamaguchi, Kunihiro Nishida, Hiroshi Inoue, Yukiko Hata, Naoki Nishida
  • Organizer: Basic Cardiovascular Sciences 2013
  • Place of Presentation: Paris Las Vegas, Las Vegas, Nevada
• [Presentation] Characterization of KCNQ1 (KV7.1, IKs) Channel Subunit with an A590T Mutation (2013)
  • Author(s): Koshi Kinoshita, Toshihide Tabata, Fukiko Ichida, Yoshiaki Yamaguchi, Kunihiro Nishida, Hiroshi Inoue, Yukiko Hata, Naoki Nishida
  • Organizer: 第77回日本循環器学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] KCNE1サブユニットのG38S変異がもたらすhERGおよびKCNQ1チャネルに対する変調作用の変化 (2013)
  • Author(s): 西出 康貴, 加藤 真理夫, 山口 由明, 木下 耕史, 藤田 陽, 野々部 雄樹, 畑 由紀子, 水牧 功一, 井上 博, 西田 尚樹, 田端 俊英
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀
• [Presentation] 遅延整流性カリウム・チャネル・サブユニット新規変異体KCNQ1(Y461X)の機能解析 (2013)
  • Author(s): 木本 克哉, 西出 康貴, 木下 耕史, 野々部 雄樹, 藤田 陽, 山口 由明, 畑 由紀子, 水牧 功一, 井上 博, 西田 尚樹, 田端 俊英
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀
• [Remarks] 研究室ホームページ
  • URL: http://www.med.u-toyama.ac.jp/legal/