Yu Ya-Feng, Wu Wen-Ying, Xiao Gen-Sheng, Shi Jian, Ling Hong-Yang
Department of Otolaryngology, The First Affiliated Hospital of Soochow University Suzhou 215006, China.
Department of Pharmacy, The First Affiliated Hospital of Soochow University Suzhou 215006, China.
Int J Clin Exp Med. 2015 Sep 15;8(9):15466-73. eCollection 2015.
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.
为探究C57BL/6J小鼠螺旋神经节神经元中T型钙通道受体的表达水平以及T型钙通道阻滞剂对42 - 44周龄C57BL/6J小鼠螺旋神经节神经元的影响。我们首先通过逆转录聚合酶链反应(RT-PCR),根据年龄对三组(6 - 8周、24 - 26周、42 - 44周)C57BL/6J小鼠螺旋神经节神经元中T型钙通道阻滞剂的亚基进行定量。接下来,我们通过灌胃给42 - 44周龄的C57BL/6J小鼠施用三种药物(唑尼沙胺、非洛地平、生理盐水),持续四周。我们观察了治疗后42 - 44周龄C57BL/6J小鼠听力阈值的变化。同时,我们测量了治疗后螺旋神经节神经元钙结合蛋白的表达。我们的结果表明,三种受体在C57BL/6J小鼠的螺旋神经节神经元中表达。α1H的表达水平强于α1G和α1I。三种受体的表达水平,尤其是α1G和α1H,随年龄显著降低。施用唑尼沙胺后,24千赫兹处的听力阈值显著降低。螺旋神经节神经元中钙结合蛋白的表达水平未观察到显著差异。有趣的是,唑尼沙胺治疗组螺旋神经节神经元中钙调蛋白的表达水平低于非洛地平和生理盐水治疗组。我们得出结论,连续四周施用T型钙通道阻滞剂可通过改善42 - 44周龄C57BL/6J小鼠螺旋神经节神经元的钙超载来改善听力。