Referenced in: none

Automatically associated channels: Kv7.4 , Slo1

Title: Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness.

Authors: Tatjana Kharkovets, Karin Dedek, Hannes Maier, Michaela Schweizer, Darina Khimich, Régis Nouvian, Vitya Vardanyan, Rudolf Leuwer, Tobias Moser, Thomas J Jentsch

Journal, date & volume: EMBO J., 2006 Feb 8 , 25, 642-52

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16437162

Abstract
KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2 dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is strongly expressed in vestibular hair cells, vestibular function appeared normal. Auditory function was only slightly impaired initially. It then declined over several weeks in Kcnq4-/- mice and over several months in mice carrying the dominant negative allele. This progressive hearing loss was paralleled by a selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the I(K,n) current of OHCs. The ensuing depolarization of OHCs impaired sound amplification. Inner hair cells and their afferent synapses remained mostly intact. These cells were only slightly depolarized and showed near-normal presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly caused by a slow degeneration of OHCs resulting from chronic depolarization.