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Reserch of relation between mechanisms of intracellular signaling pathways in cochlear outer and inner hair cells and ototoxic drugs

Research Project

Project/Area Number 13671809
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionKansai Medical University

Principal Investigator

OHNISHI Sumio  Kansai Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (80257914)

Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Keywordsouter hair cells / inner hair cells / contraction / Cl^<--> channel / actin / frosemide / MQAE / cell volume / 塩素イオンチャネル / アクチン繊維 / 細胞内塩素イオン膿度
Research Abstract

Slow shortening of cochlear outer hair cells has been speculated to modify cochlear sensitivity. Tetanic electrical field stimulation of isolated outer hair cells from guinea pigs shortened the cells for 2-3 min. Electrical stimulation reduced cell length and volume and decreased the intracellular Cl- concentration. Cytochalasin B inhibited electrical stimulation-induced shortening but not volume reduction. The following chemicals or manipulations inhibited the responses : furosemide, DIDS,AC9, tetraethylammonium, charybdotoxin (ChTX), w-conotoxin, and Ca^<2+>_free medium. These findings suggest that both electrical stimulation-induced shortening and shrinkage of outer hair cells result not only from an actin-mediated contractile force, but also from Cl- efflux through furosemide-, DIDS-, and AC9-sensitive Cl- channels, and K+ efflux through ChTX-sensitive K+ channels.
While, tetanic electrical field stimulation elicited a prominent contraction of isolated guinea pig cochlear inner hair cells. This contraction appeared 30-40 sec after field stimulation and lasted for about 1 min. Using a digital imaging microscope and the Cl^--sensitive fluorescence dye, N- (6-methoxyquinolyl) acethoethyl ester, the decrease in cell volume and intracellular Cl- concentration were concomitant with the cell contraction. Cytochalasin B inhibited this event, suggesting that the contraction is mediated by actin.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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