Differential Cochlear Hair Cell Degeneration in Mice with Impaired Potassium Recycling

CARIGNANO, C.; DIONISIO, L.; RÍAS, E.; SPITZMAUL, G.; BARILÁ, E.; AZTIRIA, E.

Paraná

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

SAIB Sociedad Argentina de Investigación bioquímica y Biología molecular

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 HC loss over time generated by absence 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 cell number average andplotted cytocochleograms. We observed the highest outer hair cell (OHC) degeneration in basal turn starting early (3 weeksold(W)), which progresses to middle and apical turns 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 turn 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.