Abstract

The endolymphatic sac (ES) is a cystic structure of the inner ear connected to the cochlea and vestibule, which plays a role in regulating ion homeostasis in inner ear fluid. Disruption of ion homeostasis can cause inner ear disorders with hearing loss and dizziness, such as Meniere’s disease. Herein, we found, for the first time, functional evidence for the involvement of β1- and β2-adrenergic receptors in apical electrogenic ion transport by human ES epithelium by using electrophysiological/pharmacological and molecular biological methods, which were dependent on K+ and Cl− ion transport. The apical electrogenic transport was absent or very weak in ES epithelia of patients with Meniere’s disease. These results suggested that adrenergic stimulation via β1- and β2-adrenergic receptors in the human ES was involved in regulation of inner ear fluid ion homeostasis and impairment of this response could be a pathological mechanism of Meniere’s disease.

Highlights

  • Β​1- and β​2-adrenergic receptors[7,11]

  • The functional evidence for the role of these receptors in inner ear fluid homeostasis and fluid volume regulation has only been provided by animal experiments[7,13,14,15,16] and there have been no reports demonstrating the functional role of the receptors in the human inner ear

  • We investigated whether Cl− channel-dependent electrogenic transport was involved in β-adrenergic stimulation-induced trans-epithelial currents, because anion transport should be balanced with the transport of cations and Cl− is the most abundant anion in the luminal fluid of the endolymphatic sac (ES)

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Summary

Introduction

Β​1- and β​2-adrenergic receptors[7,11]. These receptors were reported to exist in the luminal epithelium of the ES12. The functional evidence for the role of these receptors in inner ear fluid homeostasis and fluid volume regulation has only been provided by animal experiments[7,13,14,15,16] and there have been no reports demonstrating the functional role of the receptors in the human inner ear These adrenergic stimulation-induced changes in ion transport in the inner ear are likely to be involved in the pathophysiology of Meniere’s disease, which is an inner ear disorder characterized by recurrent vertigo attacks, sudden hearing loss, tinnitus, and aural fullness. This study can provide the first functional evidence for the role of β-adrenergic receptors in the ion homeostasis of the human inner ear and insight into a basis for the pathophysiology of Meniere’s disease

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