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率相关的耳蜗外毛细胞力生成:模型和参数估计。

Rate-dependent cochlear outer hair cell force generation: Models and parameter estimation.

机构信息

Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan.

Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Kresge Hearing Research Institute, University of Michigan, 4605 Medical Science Unit II, Ann Arbor, Michigan.

出版信息

Biophys J. 2024 Oct 1;123(19):3421-3432. doi: 10.1016/j.bpj.2024.08.007. Epub 2024 Aug 14.

Abstract

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, with two key remaining issues: the influence of the rate dependence of conformal changes in prestin and the OHC transmembrane impedance. In this paper, we mainly focus on the rate dependence of the conformal change in prestin. 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 and transmembrane impedance. Furthermore, 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.

摘要

哺乳动物耳蜗的外毛细胞 (OHC) 是一种主动的、非线性机电过程的介导者,该过程对于敏感的、频率特异性的听力是必要的。膜蛋白 prestin 赋予 OHC 一种压电样的行为,据推测这种行为可以驱动高频、逐周期的电能到机械能的转换,从而增强耳蜗对低水平声音的反应。这个假设已经争论了几十年,仍然存在两个关键问题:prestin 构象变化的速率依赖性的影响和 OHC 的跨膜阻抗。在本文中,我们主要关注 prestin 构象变化的速率依赖性。我们提出了一个 OHC 的理论机电模型,该模型明确包括构象转变的速率依赖性、粘弹性和压电性。使用该理论,我们展示了速率依赖性和粘弹性对机电力生成和跨膜阻抗的影响。此外,我们强调在估计跨膜电容时使用正确的机械边界条件的重要性。最后,描述了一组实验,这些实验从全细胞测量中唯一地估计了 OHC 的本构特性。

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