Simultaneously reduced NKCC1 and Na,K-ATPase expression in murine cochlear lateral wall contribute to conservation of endocochlear potential following a sensorineural hearing loss.
ABSTRACT The mechanisms of the response in the murine cochlear lateral wall following sensorineural hearing loss (SNHL) are poorly understood. We focused on comparing the endocochlear potential (EP) with morphological changes in the lateral wall and expression of four important potassium (K(+)) transporters in a mouse model of SNHL induced by co-administration of aminoglycoside and loop diuretic. The expression of the α1 and α2 isoforms of Na,K-ATPase, Na-K-2Cl-Cotransporter-1 (NKCC1) and potassium channel KCNQ1 was assessed. The EP showed a significant decline at 12h post-treatment followed by complete recovery by 2 days post-treatment. The EP was maintained at near normal levels in animals deafened for periods up to 112 days. Despite this recovery, there was a significant and progressive decrease in the thickness of the stria vascularis, which was predominantly due to atrophy of marginal cells. Both protein and mRNA expression of α1 and α2 isoforms of Na,K-ATPase and NKCC1 in the lateral wall were dramatically reduced following a long-term deafening. KCNQ1 expression remained unchanged. These observations provide insight into the detailed mechanisms of EP modulation following SNHL and may have crucial implications in the future treatment of aminoglycoside-induced hearing loss.
- [Show abstract] [Hide abstract]
ABSTRACT: Age-related hearing loss (ARHL) is the most common human morbidity. However, the molecular mechanisms underlying ARHL are little known. In the present study, the expression of Cav1.3 calcium channels in the C57BL/6J ARHL mouse cochlea was investigated. The hearing threshold was assessed by auditory brainstem response and the expressions of Cav1.3 calcium channels at the protein and mRNA levels were detected by immunohistochemistry, western blot, and real-time RT-PCR. Associated with the auditory brainstem response threshold increased with age, the Cav1.3 expression was gradually decreased. In comparison with 4-week-old mice, Cav1.3 expressions in the cochlea at 14, 24, and 48 weeks of age were significantly and gradually decreased at both the protein and the mRNA levels. Immunohistochemistry showed that the expression of Cav1.3 was apparently reduced at the inner hair cells, outer hair cells, and stria vascularis in the cochlear lateral wall in the aged mice. Our findings indicate that Cav1.3 calcium channel expression in the cochlea is reduced in the ARHL mice and is associated with ARHL. The data also support a view that Cav1.3 calcium channel is a good target for prevention and therapy of ARHL.Neuroreport 03/2013; · 1.40 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The C57BL/6 strain is considered an excellent model to study age-related hearing loss (AHL). Aging C57BL/6 mice are characterized by profound hearing loss but conservation of the endocochlear potential (EP). Here we show 12-month-old C57BL/6 mice display a notable hearing loss at 4, 8, 16 and 32kHz while the EP is maintained at normal level. Morphological examination shows significant outer hair cells loss in the cochlear basal turn and atrophy of the stria vascularis (SV). Fluorescence immunohistochemical studies reveal that potassium channel KCNJ10 and KCNQ1 expression dramatically decreased in the SV. Concomitant with this, mRNA levels of KCNJ10 and KCNQ1 are also reduced. In addition, three other potassium transporters, including α1-Na,K-ATPase, α2-Na,K-ATPase and NKCC1, reduce their expression at mRNA levels as well. These observations suggest that conservation of the EP in aging C57BL/6 mice is attributable to the SV generating a new balance for potassium influx and efflux at a relatively lower level.Neuroscience Letters 09/2013; · 2.03 Impact Factor