DIFFERENTIAL COCHLEAR HAIR CELL DEGENERATION IN MICE WITH IMPAIRED POTASSIUM RECYCLING

CARIGNANO C; BARILA E; RIAS E; DIONISIO, L.; AZTIRIA E; SPITZMAUL, G.

Paraná

Congreso; LIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2018

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

Potassium ion (K+) is essential for sound transduction in mammalian inner ear. KCNQ4, a voltage-gated K+ channel, is expressed in cochlear hair cells (HCs) and in the central auditory pathway. KCNQ4 mutations lead to DFNA2, a progressive sensorineural deafness, due to chronic depolarization of HCs. Our aim is to analyze the progression of HCs loss over time generated by deletion of KCNQ4 channel in a mouse model lacking its expression (Kcnq4-/-). Quantitative PCR on wild-type mouse revealed the strongest Kcnq4 mRNA level in basal cochlear turn, while it decreases 50% in middle-apical turns. By using immunofluorescence on cochlear whole-mounts, we estimated the cell number and plotted cytocochleograms. We observed the highest outer hair cell (OHC) degeneration in basal turn starting early (3 weeks-old (W)) that progress to middle and apical segments in older mice (10-58W). Moreover, cell death progression correlated with different OHC stereociliar disarrangement patterns. Degeneration differed according to OHC row: the middle one exhibited the maximum decrease at 10W in Kcnq4-/- mice. Furthermore, inner HCs reached total loss in basal initial segment at 40W and cell loss, also progresses to middle segments with age. Our results indicate that both HCs degenerate but starting at different ages, contributing to elucidate the mechanisms leading to profound hearing loss in DFNA2 patients.