Wang Xiang, Jia Shuping, Currall Benjamin, Yang Shiming, He David Z Z
Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA.
Hear Res. 2007 Dec;234(1-2):52-8. doi: 10.1016/j.heares.2007.09.001. Epub 2007 Sep 25.
The cochlear outer hair cell (OHC), which plays a crucial role in mammalian hearing through its unique voltage-dependent motility, has been established as a primary target of the ototoxicity of aminoglycoside antibiotics. These polycationic drugs are also known to block a wide variety of ion channels, purinergic ionotropic channels, and nicotinic ACh receptors in hair cells in vitro. The OHC motor protein, prestin, is a voltage-sensitive transmembrane protein containing several negatively charged residues on both intra- and extracellular surface. The acidic sites may be susceptible to polycationic-charged aminoglycoside binding, which may result in disruption of motility. We attempted to examine whether aminoglycosides such as streptomycin and gentamicin could affect OHC motility and its electrical signature, the nonlinear capacitance (NLC) in adult gerbil OHCs. Somatic motility and NLC were measured under the whole-cell voltage-clamp mode. Streptomycin and gentamicin were applied extracellularly or intracellularly. Results show that streptomycin and gentamicin did not change either the magnitude of motility or the NLC. Theses results suggest that, although streptomycin and gentamicin can block mechanotransduction channels as well as ACh receptors in hair cells, they have no direct affect on OHC somatic motility.
耳蜗外毛细胞（OHC）通过其独特的电压依赖性运动在哺乳动物听力中发挥关键作用，已被确定为氨基糖苷类抗生素耳毒性的主要靶点。这些聚阳离子药物在体外也已知会阻断毛细胞中的多种离子通道、嘌呤能离子通道和烟碱型乙酰胆碱受体。OHC运动蛋白prestin是一种电压敏感的跨膜蛋白，在细胞内和细胞外表面均含有多个带负电荷的残基。这些酸性位点可能易受带聚阳离子电荷的氨基糖苷类药物结合的影响，这可能导致运动功能的破坏。我们试图研究链霉素和庆大霉素等氨基糖苷类药物是否会影响成年沙鼠OHC的运动及其电信号——非线性电容（NLC）。在全细胞电压钳模式下测量体细胞运动和NLC。链霉素和庆大霉素通过细胞外或细胞内给药。结果表明，链霉素和庆大霉素既没有改变运动幅度，也没有改变NLC。这些结果表明，尽管链霉素和庆大霉素可以阻断毛细胞中的机械转导通道以及乙酰胆碱受体，但它们对OHC体细胞运动没有直接影响。
