ABSTRACT
The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6-8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24-26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24-26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected.
ABSTRACT
To explore the expression levels of T-type calcium channel receptors in spiral ganglion neurons of C57BL/6J mice and the effect of T-type calcium channel blockers on the spiral ganglion neurons of 42-44-W C57BL/6J mice. We first quantified the subunits of T-type calcium channel blockers in the spiral ganglion neurons of C57BL/6J mice in three groups (6-8 W, 24-26 W, 42-44 W) according to age via RT-PCR. Next, we administered three drugs (zonisamide, felodipine, saline) to the 42-44-W C57BL/6J mice by gavage for four weeks. We observed the changes in the hearing threshold of 42-44-W C57BL/6J mice after treatment. Meanwhile, we measured the expression of calcium-binding proteins of spiral ganglion neurons after treatment. Our results showed that three receptors were expressed in the spiral ganglion neurons of C57BL/6J mice. The expression level of α1H was stronger than that of α1G and α1I. The expression levels of three receptors especially for α1G and α1H significantly decreased with age. The hearing threshold at 24 kHz was significantly decreased after zonisamide administration. No significant difference in the expression level of calbindin in spiral ganglion neurons was noted. Interestingly, the expression level of calmodulin in spiral ganglion neurons was lower in the zonisamide-treated groups than in the felodipine- and saline-treated group. We concluded that the administration of T-type calcium channel blocker for four consecutive weeks can improve the hearing by ameliorating calcium overload on spiral ganglion neurons of 42-44-W C57BL/6J mice.
