人类耳蜗外侧壁频率依赖性电化学梯度的结构与分子证据

文献信息

中文摘要

目的： 血管纹（SV）是衬于人类耳蜗外侧壁（LW）的三部分上皮，产生对听觉感觉转导至关重要的正性耳蜗内电位（EP）。关于其沿耳蜗螺旋的可变结构和组织，或是否存在电化学梯度，目前信息有限。在此，我们使用三维（3D）同步辐射相位对比成像（SR-PCI）以及光学和透射电子显微镜（LM和TEM），基于SR-PCI在不同频率位置检查人类SV和螺旋韧带（SL）。结果与我们实验室最近进行的分子分析进行了比较。
方法： 基于Greenwood公式匹配的耳蜗频率图，在不同频率位置对LW和SV进行体积和微解剖分析，包括关键K+再循环通路。TEM分析与先前获得的离子转运蛋白和通道表达结果相关联，包括多重RNAscope®技术。
结果： 在耳蜗顶转，LW体积缩小100倍，SV缩小14倍。超微结构分析显示SV和SL中细胞减少。此外，SV细胞和血管模式的组织和结构沿耳蜗螺旋发生改变。Claudius细胞轮廓、TEM以及先前Na/K-ATPase活性和GJB2基因转录物分布的结果表明，顶转耳蜗LW中K+再循环潜力和水通量降低。
结论： 宏观、微观和最近的分子解剖学研究表明，人类耳蜗“电池”在顶部可能效力较低。这可能表明低频感觉转导可能部分由更基底区域驱动。电化学的频率依赖性变化可能与代谢性听力损失和人工耳蜗植入等手术治疗具有病理生理学意义。

英文摘要

PURPOSE: The stria vascularis (SV) is a tripartite epithelium lining the lateral wall (LW) of the human cochlea, generating a positive endocochlear potential (EP) essential for auditory sensory transduction. There remains limited information about its variable structure and organization along the cochlear spiral or whether an electrochemical gradient exists. Here, we used three-dimensional (3D) synchrotron radiation phase-contrast imaging (SR-PCI) and light and transmission electron microscopy (LM and TEM) to examine the human SV and spiral ligament (SL) at different frequency locations based on the SR-PCI. Results were compared with recent molecular analyses performed in our laboratory.
METHODS: Volumetric and microanatomic analyses of the LW and SV, including critical K+ recycling pathways were made at different frequency locations on matched cochlear frequency maps based on Greenwood's formula. TEM analyses were correlated with previous results obtained on the expression of ion transporter and channels including the multiplex RNAscope® technique.
RESULTS: The LW diminished in volume a 100-fold and the SV 14-fold in the cochlear apical turn. Ultrastructural analyses showed reduced cellularity in the SV and SL. Moreover, the organization and architecture of the SV cell and vascular pattern modified along the cochlear spiral. Claudius cell outline, TEM, and prior results of Na/K-ATPase activity and GJB2 gene transcript distribution suggest there is a reduced K+ recycling potential and water flux in the LW of the apical cochlea.
CONCLUSION: Macro-, micro-, and recent molecular anatomical studies suggest that the human cochlear "battery" may be less potent in the apex. This could indicate that sensory transduction at low frequencies may be partially power-driven by more basal regions. Frequency-dependent variations in electrochemistry may have pathophysiological significance in connection with metabolic hearing loss and surgical treatments such as cochlear implantation.