Expression of Na/K-ATPase subunits in the human cochlea: a confocal and super-resolution microscopy study with special reference to auditory nerve excitation and cochlear implantation

Wei Liu,Maria Luque,Rudolf Glueckert,Niklas Danckwardt-Lillieström,Charlotta Kämpfe Nordström,Anneliese Schrott-Fischer,Helge Rask-Andersen

doi:10.1080/03009734.2019.1653408

Abstract

Background: For the first time the expression of the ion transport protein sodium/potassium-ATPase and its isoforms was analyzed in the human cochlea using light- and confocal microscopy as well as super-resolution structured illumination microscopy. It may increase our understanding of its role in the propagation and processing of action potentials in the human auditory nerve and how electric nerve responses are elicited from auditory prostheses.Material and methods: Archival human cochlear sections were obtained from trans-cochlear surgeries. Antibodies against the Na/K-ATPase β1 isoform together with α1 and α3 were used for immunohistochemistry. An algorithm was applied to assess the expression in various domains.Results: Na/K ATPase β1 subunit was expressed, mostly combined with the α1 isoform. Neurons expressed the β1 subunit combined with α3, while satellite glial cells expressed the α1 isoform without recognized association with β1. Types I and II spiral ganglion neurons and efferent fibers expressed the Na/K-ATPase α3 subunit. Inner hair cells, nerve fibers underneath, and efferent and afferent fibers in the organ of Corti also expressed α1. The highest activity of Na/K-ATPase β1 was at the inner hair cell/nerve junction and spiral prominence.Conclusion: The human auditory nerve displays distinct morphologic features represented in its molecular expression. It was found that electric signals generated via hair cells may not go uninterrupted across the spiral ganglion, but are locally processed. This may be related to particular filtering properties in the human acoustic pathway.

Highlights

The human inner ear is difficult to study due to its exceptional fragility and the surrounding hard bone, and there are few descriptions of its molecular physiognomies
Prominent Na/K-ATPase b1 expression was noted at the spiral prominence, marginal cells of the stria vascularis, types II, IV, and V fibrocytes, spiral ganglion neurons, nerves in the organ of Corti (Figure 3), dendrites, axons, interdental cells of the spiral limbus, basolateral cell membranes of the supporting cells (Deiters and Hensen cells), Boettcher and Claudius cells, and outer and inner sulcus cells
Scanning electron microscopy showed the outer spiral bundle as well as the nerve fibers entering the organ of Corti in man (Figures 3(B–E)). b1 Expression in fibers of the outer spiral bundle was found using super-resolution structured illumination microscopy (SR-SIM) (inset of Figure 3(C))

Summary

Introduction

The human inner ear is difficult to study due to its exceptional fragility and the surrounding hard bone, and there are few descriptions of its molecular physiognomies. We used super-resolution structured illumination microscopy (SR-SIM) to analyze the molecular structure of the human ion machinery in the lateral cochlear wall [2] This unique tissue generates the endo-cochlear potential essential for mechanic-electric transduction [3,4]. For the first time the expression of the ion transport protein sodium/potassium-ATPase and its isoforms was analyzed in the human cochlea using light- and confocal microscopy as well as super-resolution structured illumination microscopy. It may increase our understanding of its role in the propagation and processing of action potentials in the human auditory nerve and how electric nerve responses are elicited from auditory prostheses. This may be related to particular filtering properties in the human acoustic pathway

Methods

Results

Conclusion