Potassium-induced release of an endogenous toxic activity for outer hair cells and auditory neurons in the cochlea: a new pathophysiological mechanism in Menière's disease?

In Menière's disease, the increase of extracellular potassium concentration in the perilymph is thought to play a key role in determining the progressive loss of cochlear hair cells. In this paper, we describe a serum-free culture preparation of hair cells from 5 day-old rat and report the release by the cochlea, in response to an increase of extracellular potassium concentration, of a cytotoxic activity active on hair cells and auditory neurons. The toxic activity is associated with low molecular weight (less than 10,000 Dalton) molecule(s) as revealed by ultrafiltration. Morphological studies performed on the organ of Corti incubated during 24 h in the presence of the cochlea-derived toxic activity (CTA), show that this factor is toxic for hair cells and not for supporting or surrounding cells. The release of CTA occurs both in the spiral ganglion and in the organ of Corti. We suggest that this cochlea-derived toxic activity may play an important role in the pathophysiology of the hearing loss that occurs during the progression of Menière's disease.