β1- and β2-adrenergic stimulation-induced electrogenic transport by human endolymphatic sac epithelium and its clinical implications

Sci Rep. 2017 Feb 6:7:42217. doi: 10.1038/srep42217.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Adrenergic beta-1 Receptor Antagonists / pharmacology
  • Adrenergic beta-2 Receptor Antagonists / pharmacology
  • Barium / pharmacology
  • Biological Transport / drug effects
  • Endolymphatic Sac / drug effects
  • Endolymphatic Sac / metabolism*
  • Endolymphatic Sac / pathology
  • Epithelium / drug effects
  • Epithelium / metabolism*
  • Epithelium / pathology
  • Female
  • Humans
  • Isoproterenol / pharmacology
  • Male
  • Meniere Disease / pathology
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism*

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Barium
  • Isoproterenol
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid