Amplification mode differs alongthe length of the mouse cochlea as revealed by connexin 26 deletion from specific gap junctions

The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters’ cells (DCs) and pillar cells (PCs), coupled by gapjunctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knockout (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-drivingvoltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses. However, the Cx26 cKO desensitizes mid-high-frequency DPOAEs and active BM responses and sensitizes low-mid-frequency neural excitation. This functional segregation may indicate that the flexible, apical turn cochlear partition facilitates transfer of OHC displacements (isotonic forces) for cochlear amplification and neural excitation. DC and PC Cx26 expression is essential for cochlear amplification in the stiff basal turn, possibly through maintaining cochlear partition mechanical impedance, thereby ensuring effective transfer of OHC isometric forces.

哺乳动物耳蜗（mammalian cochlea）具备敏锐的频率调谐特性与极致的感知灵敏度，这源于外毛细胞（outer hair cells, OHCs）向耳蜗分区（cochlear partition）传递的主动力。该力的传递由特化细胞介导并调控，包括迪特尔斯细胞（Deiters’ cells, DCs）与柱细胞（pillar cells, PCs），这些细胞通过由连接蛋白26（connexin 26, Cx26）和连接蛋白30（Cx30）构成的缝隙连接（gap junctions）实现耦联。我们构建了在迪特尔斯细胞与柱细胞中条件性敲除Cx26（conditional Cx26 knockout, Cx26 cKO）的小鼠模型，该模型的感觉转导（sensory transduction）、感受器电流驱动电压、中低频畸变产物耳声发射（distortion-product-otoacoustic-emissions, DPOAEs）以及被动基底膜（basilar membrane, BM）反应均未受影响。然而，该Cx26条件性敲除模型会使中高频畸变产物耳声发射与主动基底膜反应出现脱敏现象，同时增强中低频的神经兴奋。这种功能分离现象或许表明，具有弹性的耳蜗顶回分区能够促进外毛细胞位移（等张力，isotonic forces）的传递，以实现耳蜗放大与神经兴奋过程。迪特尔斯细胞与柱细胞的Cx26表达对于坚硬的耳蜗底回的耳蜗放大功能至关重要，这一过程可能通过维持耳蜗分区的机械阻抗（mechanical impedance）实现，从而确保外毛细胞等长力（isometric forces）的有效传递。