Abstract

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K+ channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K+ channels in the electrogenic transport of human ES epithelium. The identified K+ channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K+ transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid.

Highlights

  • David Geffen School of Medicine, University of California Los Angeles, 2100 W

  • It has been thought that various ion transport activities in endolymphatic sac (ES) play an important role in regulating ion homeostasis of the inner ear; there have been no reports of a functional experiment for ion transport in human ES epithelium

  • We measured the net physiologic trans-epithelial current that is produced by various ion channels in the human ES epithelium harvested during acoustic tumour surgery instead of measuring the current that is produced by a single cell because the specific cell types could not be identified during the measurement, and the net trans-epithelial current is more indicative of whole-organ function

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Summary

Introduction

David Geffen School of Medicine, University of California Los Angeles, 2100 W. Transporters, and exchangers have been reported in ES epithelium only by animal or cultured cell experiments: a highly Na+-permeable non-selective cation channel, Na+-Cl− co-transporter, Na+-K+-2Cl− co-transporter (NKCC), epithelial Na+ channel (ENaC), Na+-H+ exchanger (NHE), pendrin, and H+-ATPase on the apical side and Na+, K+-ATPase and K+ channels on the basolateral side[12]. We measured the net physiologic trans-epithelial current that is produced by various ion channels in the human ES epithelium harvested during acoustic tumour surgery instead of measuring the current that is produced by a single cell because the specific cell types could not be identified during the measurement, and the net trans-epithelial current is more indicative of whole-organ function. The results of this study may contribute to the elucidation of the role of human ES in the regulation of inner ear ion homeostasis, which is essential for maintaining normal hearing and balance functions

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