Cai Wen, Grosh Karl
bioRxiv. 2023 Dec 14:2023.12.13.571371. doi: 10.1101/2023.12.13.571371.
The outer hair cells (OHCs) of the mammalian cochlea are the mediators of an active, nonlinear electromechanical process necessary for sensitive, frequency specific hearing. The membrane protein prestin conveys to the OHC a piezoelectric-like behavior hypothesized to actuate a high frequency, cycle-by-cycle conversion of electrical to mechanical energy to boost cochlear responses to low-level sound. This hypothesis has been debated for decades, and we address two key remaining issues: the influence of the rate dependence of conformal changes in prestin and the OHC transmembrane impedance. We develop a theoretical electromechanical model of the OHC that explicitly includes rate dependence of conformal transitions, viscoelasticity, and piezoelectricity. Using this theory, we show the influence of rate dependence and viscoelasticity on electromechanical force generation. Further, we stress the importance of using the correct mechanical boundary conditions when estimating the transmembrane capacitance. Finally, a set of experiments is described to uniquely estimate the constitutive properties of the OHC from whole-cell measurements.
哺乳动物耳蜗的外毛细胞(OHC)是一种主动、非线性机电过程的介导者,这一过程对于灵敏的、频率特异性听觉是必需的。膜蛋白prestin赋予OHC一种类似压电的行为,据推测这种行为可驱动电到机械能的高频逐周期转换,以增强耳蜗对低强度声音的反应。这一假设已争论了数十年,我们解决了两个尚存的关键问题:prestin中构象变化的速率依赖性以及OHC跨膜阻抗的影响。我们建立了一个OHC的理论机电模型,该模型明确包含了构象转变的速率依赖性、粘弹性和压电性。利用这一理论,我们展示了速率依赖性和粘弹性对机电力产生的影响。此外,我们强调了在估计跨膜电容时使用正确机械边界条件的重要性。最后,描述了一组实验,以从全细胞测量中唯一地估计OHC的本构特性。