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

已经推测耳蜗外毛细胞的缓慢缩短改变耳蜗敏感性。强直电场刺激豚鼠离体外毛细胞缩短细胞2-3分钟。电刺激减少细胞长度和体积，降低细胞内Cl-浓度。细胞松弛素B抑制电刺激诱导的缩短，但不体积减小。以下化学物质或操作抑制反应：呋塞米、DIDS、AC 9、四乙基铵、Charybdotoxin（ChTX）、ω-芋螺毒素和无Ca^<2+>_培养基。这些结果表明，电刺激引起的外毛细胞缩短和收缩不仅是肌动蛋白介导的收缩力的结果，而且还可能是通过速尿、DIDS和AC 9敏感的Cl-通道和ChTX敏感的K+通道的Cl-外排和K+外排的结果。这种收缩在电场刺激后30-40秒出现，持续约1分钟。使用数字成像显微镜和Cl^-敏感的荧光染料N-（6-甲氧基喹啉基）乙酰乙基酯，细胞体积和细胞内Cl-浓度的减少伴随着细胞收缩。细胞松弛素B抑制了这一事件，表明收缩是由肌动蛋白介导的。

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.