Caruso Department of Otolaryngology - Head and Neck Surgery, University of Southern California, Los Angeles, CA, USA.
VA Loma Linda Healthcare System, Loma Linda, CA, USA.
Hear Res. 2022 Sep 15;423:108473. doi: 10.1016/j.heares.2022.108473. Epub 2022 Mar 1.
Along with outer hair cell (OHC) somatic electromotility as the actuator of cochlear amplification, active hair bundle motility may be a complementary mechanism in the mammalian auditory system. Here, we searched the mouse cochlea for the presence of spontaneous bundle oscillations that have been observed in non-mammalian ears. In those systems, removal of the overlying membrane is necessary for spontaneous bundle oscillations to manifest. Thus, we used a genetic mouse model with a C1509G (cysteine-to-glycine) point mutation in the Tecta gene where the tectorial (TM) is lifted away from the OHC bundles, allowing us to explore whether unloaded bundles spontaneously oscillate. We used VOCTV in vivo to detect OHC length changes due to electromotility as a proxy for the spontaneous opening and closing of the mechanoelectrical transduction (MET) channels associated with bundle oscillation. In wild type mice with the TM attached to OHC bundles, we did find peaks in vibratory magnitude spectra. Such peaks were not observed in the mutants where the TM is detached from the OHC bundles. Statistical analysis of the time signals indicates that these peaks do not signify active oscillations. Rather, they are filtered responses of the sensitive wild type cochlea to weak background noise. We therefore conclude that, to the limits of our system (∼30 pm), there is no spontaneous mechanical activity that manifests as oscillations in OHC electromotility within the mouse cochlea, arguing that unloaded OHC bundles do not oscillate in vivo. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.
除了外毛细胞(OHC)体细胞电活动作为耳蜗放大的致动器之外,主动毛束运动可能是哺乳动物听觉系统中的一种补充机制。在这里,我们在小鼠耳蜗中寻找了已经在非哺乳动物耳朵中观察到的自发束振动。在这些系统中,去除覆盖膜是自发束振动表现所必需的。因此,我们使用了一种带有 C1509G(半胱氨酸到甘氨酸)点突变的 Tecta 基因的遗传小鼠模型,其中的盖膜(TM)从 OHC 束上抬起,使我们能够探索未加载的束是否会自发振动。我们使用 VOCTV 在体内检测由于电活动引起的 OHC 长度变化,作为与束振动相关的机械电转换(MET)通道自发打开和关闭的代理。在 TM 附着在 OHC 束上的野生型小鼠中,我们确实在振动幅度谱中发现了峰值。在 TM 从 OHC 束上分离的突变体中,没有观察到这种峰值。对时间信号的统计分析表明,这些峰值并不表示主动振动。相反,它们是敏感的野生型耳蜗对弱背景噪声的滤波响应。因此,我们得出结论,在我们的系统(约 30 pm)的限制内,没有自发的机械活动表现为 OHC 电活动中的振动,这表明未加载的 OHC 束在体内不会振动。本文是由 Joseph Santos-Sacchi 和 Kumar Navaratnam 编辑的特刊《外毛细胞》的一部分。