DIFFERENTIAL COCHLEAR HAIR CELL DEGENERATION IN MICE WITH IMPAIRED POTASSIUM RECYCLING

CARIGNANO CAMILA; BARILA ESTEBAN; RÍAS EZEQUIEL; DIONISIO LEONARDO; ,AZTIRIA EUGENIO; SPITZMAUL GUILLERMO

Paraná

Congreso; 54th Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology; 2018

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 haircells (HCs) and in the central auditory pathway. KCNQ4 mutations lead to DFNA2, a progressive sensorineural deafness, due to chronicdepolarization of HCs. Our aim is to analyze the progression of HC loss over time generated by absence of KCNQ4 channel in a mouse modellacking its expression (Kcnq4-/-). Quantitative PCR on wild-type mouse revealed the strongest Kcnq4 mRNA level in basal cochlear turn, whileit 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)), whichprogresses to middle and apical turns in older mice (10-58W). Moreover, cell death progression correlated with different OHC stereociliardisarrangement 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 resultsindicate that both HCs degenerate but starting at different ages, contributing to elucidate the mechanisms leading to profound hearing loss inDFNA2 patients.