KCNQ4, a novel potassium channel expressed in sensory outer hair cells, ismutated in dominant deafness

Potassium channels regulate electrical signaling and the ionic composition of biological fluids. Mutations in the three known genes of the KCNQ branch of the K+ channel gene family underlie inherited cardiac arrhythmias (in s ome cases associated with deafness) and neonatal epilepsy. We have now clon ed KCNQ4, a novel member of this branch. It maps to the DFNA2 locus for a f orm of nonsyndromic dominant deafness. In the cochlea, it is expressed in s ensory outer hair cells, A mutation in this gene in a DFNA2 pedigree change s a residue in the KCNQ4 pore region. It abolishes the potassium currents o f wild-type KCNQ4 on which it exerts a strong dominant-negative effect. Whe reas mutations in KCNQ1 cause deafness by affecting endolymph secretion, th e mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hai r cells.