2004 Fiscal Year Final Research Report Summary
Reserch of relation between mechanisms of intracellular signaling pathways in cochlear outer and inner hair cells and ototoxic drugs
| Project/Area Number |
13671809
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
OHNISHI Sumio Kansai Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (80257914)
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| Project Period (FY) |
2001 – 2004
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| Keywords | outer hair cells / inner hair cells / contraction / Cl^<--> channel / actin / frosemide / MQAE / cell volume |
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| 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.
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