Zhu Zenghao, Reid Wisam, Ó Maoiléidigh Dáibhid
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, 94304, CA, USA.
Harvard Medical School, Harvard University, Boston, 02114, MA, USA.
Sci Rep. 2024 Dec 2;14(1):29904. doi: 10.1038/s41598-024-81355-5.
In our ears, outer-hair-cell bundles (OHBs) convert sound-induced forces into receptor currents that drive cochlear amplification, the process responsible for the micropascal-scale threshold and million-fold dynamic range of hearing. OHBs rely on gating springs to open mechanoelectrical-transduction (MET) ion channels, through which the receptor current flows. OHBs have larger gating-spring stiffnesses than other types of hair bundles, but we have a poor understanding of how gating-spring stiffness contributes to OHB mechanics and receptor-current regulation. Using experimentally-constrained mathematical models of the OHB, we show that the increased gating-spring stiffness in an OHB increases its stiffness and damping. The OHB's 3D morphology reduces the contribution of gating-spring stiffness to OHB stiffness, reduces the contribution of MET-channel gating to OHB stiffness and damping, but causes additional OHB damping that rises with gating-spring stiffness. Gating-spring stiffness increases the OHB's receptor current but decreases its displacement-current dynamic range. Strikingly, the OHB's 3D morphology causes its force-current dynamic range to decrease with gating-spring stiffness. Our results suggest a trade-off between threshold and dynamic range regulated by OHB gating-spring stiffness.
在我们的耳朵中,外毛细胞束(OHBs)将声音诱导的力转化为驱动耳蜗放大的受体电流,耳蜗放大是一种负责听力中微帕斯卡级阈值和百万倍动态范围的过程。OHBs依靠门控弹簧来打开机械电转导(MET)离子通道,受体电流通过该通道流动。OHBs的门控弹簧刚度比其他类型的毛细胞束更大,但我们对门控弹簧刚度如何影响OHB力学和受体电流调节了解甚少。通过使用OHB的实验约束数学模型,我们表明OHB中增加的门控弹簧刚度会增加其刚度和阻尼。OHB的三维形态降低了门控弹簧刚度对OHB刚度的贡献,降低了MET通道门控对OHB刚度和阻尼的贡献,但会导致随门控弹簧刚度增加的额外OHB阻尼。门控弹簧刚度增加了OHB的受体电流,但降低了其位移电流动态范围。引人注目的是,OHB的三维形态导致其力电流动态范围随门控弹簧刚度而降低。我们的结果表明,OHB门控弹簧刚度调节的阈值和动态范围之间存在权衡。