KCNQ1/KCNE1 potassium channels in mammalian vestibular dark cells

• Published in: Hearing research 2001-03, Vol.153 (1), p.132-145
• Main Authors: Nicolas, Marie-Thérèse, Demêmes, Danielle, Martin, Agnès, Kupershmidt, Sabina, Barhanin, Jacques
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Dark cell; DNA Primers - genetics; Electron microscopy; Fundamental and applied biological sciences. Psychology; Humans; Immunocytochemistry; Immunohistochemistry; In Situ Hybridization; KCNQ Potassium Channels; KCNQ1 Potassium Channel; KCNQ1/KCNE1 (KvLQT1/IsK); Knock-out mouse; Long QT Syndrome - genetics; Long QT Syndrome - metabolism; Long QT Syndrome - pathology; Mice; Mice, Knockout; Microscopy, Electron; Molecular Sequence Data; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Mutation; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Voltage-Gated; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vertebrates: nervous system and sense organs; Vestibule, Labyrinth - cytology; Vestibule, Labyrinth - growth & development; Vestibule, Labyrinth - metabolism
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(00)00268-9

The high [K +] in the inner ear endolymph is essential for mechanosensory transduction in hearing and balance. Several ion channels, including a slowly activating, voltage-dependent, outwardly conducting K + channel composed of the KCNQ1 (KvLQT1) and KCNE1 (IsK/minK) subunits, are expressed at the apical surface of vestibular dark cells. We investigated the underlying molecular mechanisms of this conductance using in situ hybridization, RT-PCR, and immunocytochemistry and by tracking the ultrastructural changes of vestibular structures in kcne1(−/−) mice. In the wild type mice, the KCNE1 and KCNQ1 proteins are expressed specifically at the apical membrane of dark cells, as early as gestational day (GD) 17 for KCNE1 while KCNQ1 mRNAs can be detected at GD 18. This is the first demonstration that the two protein components of this potassium channel co-localize in a polarized fashion at the cellular level. Although the vestibular end-organs are normal at birth in kcne1(−/−) mice, they begin to show modifications during postnatal development: we observed an increase in the height of the dark cells, in their number of mitochondria, and in basolateral membrane infoldings. Subsequently, the epithelium degenerates and the endolymphatic space collapses. Similar changes are known to occur in the cardio-auditory Jervell–Lange-Nielsen syndrome which is caused by mutations in the same channel.