Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Mechanoelectrical Transduction Channels

• Project/Area Number: 26462551
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAWASHIMA Yoshiyuki 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (10376759)
• Co-Investigator(Kenkyū-buntansha): 野口 佳裕 信州大学, 医学部, 特任教授 (50282752)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 内耳 / 有毛細胞 / アミノグリコシド系抗菌薬 / TMC1 / TMC2 / 内耳有毛細胞 / 機会電気変換イオンチャネル / 機械電気変換イオンチャネル / アミノ

Outline of Final Research Achievements

Systemically administered aminoglycoside antibiotics enter the inner ear hair cells and trigger apoptosis. However, the in vivo mechanisms by which aminoglycoside antibiotics enter hair cells remain controversial. Transmembrane channel-like 1 (TMC1) and TMC2 are essential for MET and are components of the stereocilia MET channel complex. The present study aimed to clarify that systemic fluorescent gentamicin enters mouse hair cells through MET channels. Gentamicin-conjugated Texas Red (GTTR) or PBS was subcutaneously injected into Tmc1Δ;Tmc2Δ mice and wild-type mice at postnatal day 0 (P0), P2, P4, or P6. In Tmc1Δ;Tmc2Δ mice, the intensity was mostly stable from P0 through P6. In wild-type mice, the GTTR fluorescent intensity gradually increased with the development of hair cells. The increase in the GTTR intensity in wild-type mice coincided with the spatiotemporal onset of MET. These results provide evidence that AGs enter hair cells predominantly through MET channels.

Research Products

• [Presentation] Systemically Administered Gentamicin Enters Neonatal Mouse cochlear Hair Cells Predominantly Through Mechanoelectrical Transduction Channels (2018)
  • Author(s): Ayane Makabe, Yoshiyuki Kawashima, Taro Fujikawa, Taku Ito, Takeshi Tsutsumi
  • Organizer: 17th Korea Japan Joint Meeting of Otorhinolaryngology Head and Neck Surgery
  • Int'l Joint Research
• [Presentation] Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Mechanoelectrical Transduction Channels (2017)
  • Author(s): Ayana Makabe, Yoshiyuki Kawashima, Ayako Maruyama, Kiyoto Kurima, Andrew Griffith, Takeshi Tsutsumi
  • Organizer: Association for Research in Otolaryngology 40th Annual MidWinter Meeting
  • Place of Presentation: Baltimore, Maryland, USA
  • Year and Date: 2017-02-11
  • Int'l Joint Research
• [Presentation] Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Mechanoelectrical Transduction Channels (2017)
  • Author(s): Ayane Makabe, Yoshiyuki Kawashima, Ayako Maruyama, Kiyoto Kurima, Andrew Griffith, Takashi Tsutumi
  • Organizer: 40th Association for Research in Otolaryngology Annual Mid Winter Meeting
  • Int'l Joint Research
• [Presentation] 全身投与されたアミノグリコシド系抗菌薬の内耳有毛細胞への進入経路の解明 (2017)
  • Author(s): 真壁彩音、川島慶之、来間清人、丸山絢子、伊藤 卓、藤川太郎、堤 剛
  • Organizer: 第27回 日本耳科学会総会・学術講演会