KCNQ1/KCNE1 potassium channels in mammalian vestibular dark cells

The high [K+] in the inner ear endolymph is essential for mechanosensory tr ansduction 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 api cal surface of vestibular dark cells. We investigated the underlying molecu lar mechanisms of this conductance using in situ hybridization, RT-PCR, and immunocytochemistry and by tracking the ultrastructural changes of vestibu lar structures in kcne1(-/-) mice. In the wild type mice, the KCNE1 and KCN Q1 proteins are expressed specifically at the epical membrane of dark cells , as early as gestational day (GD) 17 for KCNE1 while KCNQ1 mRNAs can be de tected at GD 18. This is the first demonstration that the two protein compo nents of this potassium channel co-localize in a polarized fashion at the c ellular level. Although the vestibular end-organs are normal at birth in kc ne1(-/-) mice, they begin to show modifications during postnatal developmen t: 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 chan ges are known to occur in the cardio-auditory Jervell-Lange-Nielsen syndrom e which is caused by mutations in the same channel. (C) 2001 Published by E lsevier Science B.V.