Ludwig J, Oliver D, Frank G, Klöcker N, Gummer A W, Fakler B
Department of Physiology II, Ob dem Himmelreich 7, 72074 Tübingen, Germany.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4178-83. doi: 10.1073/pnas.071613498.
Cochlear outer hair cells (OHCs) are responsible for the exquisite sensitivity, dynamic range, and frequency-resolving capacity of the mammalian hearing organ. These unique cells respond to an electrical stimulus with a cycle-by-cycle change in cell length that is mediated by molecular motors in the cells' basolateral membrane. Recent work identified prestin, a protein with similarity to pendrin-related anion transporters, as the OHC motor molecule. Here we show that heterologously expressed prestin from rat OHCs (rprestin) exhibits reciprocal electromechanical properties as known for the OHC motor protein. Upon electrical stimulation in the microchamber configuration, rprestin generates mechanical force with constant amplitude and phase up to a stimulus frequency of at least 20 kHz. Mechanical stimulation of rprestin in excised outside-out patches shifts the voltage dependence of the nonlinear capacitance characterizing the electrical properties of the molecule. The results indicate that rprestin is a molecular motor that displays reciprocal electromechanical properties over the entire frequency range relevant for mammalian hearing.
耳蜗外毛细胞(OHCs)负责哺乳动物听觉器官的高灵敏度、动态范围和频率分辨能力。这些独特的细胞对电刺激的反应是细胞长度逐周期变化,这是由细胞基底外侧膜中的分子马达介导的。最近的研究确定了一种与pendrin相关阴离子转运体相似的蛋白质——prestin,作为外毛细胞的马达分子。在这里,我们表明,从大鼠外毛细胞(rprestin)中异源表达的prestin表现出与已知的外毛细胞马达蛋白相反的机电特性。在微腔配置中进行电刺激时,rprestin会产生振幅和相位恒定的机械力,刺激频率至少可达20kHz。在切除的外翻膜片中对rprestin进行机械刺激会改变表征该分子电学特性的非线性电容的电压依赖性。结果表明,rprestin是一种分子马达,在与哺乳动物听力相关的整个频率范围内都表现出相反的机电特性。