Structural and Molecular Evidence for a Frequency-Dependent Electrochemical Gradient in the Human Cochlear Lateral Wall

Abstract 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.