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

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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.