On the role of subtypes of muscarinic receptors in the inner ear

今年，我们在过去两年所建立的基础上继续我们的研究。然而，年初我们遇到了两个麻烦。首先，由于流行病的问题，敲除动物的供应中断了大约半年。11月恢复了稳定的供应，我们恢复了实验。其次，与此同时，美国的一个竞争实验室报告说，他们缺乏毒蕈碱受体的小鼠（与我们的敲除无关的产物）具有几乎正常的听力和对耳毒性剂的相似敏感性（Maison SF，et al. 2005）。首先，我们修改了记录OAE的计算机软件，这是去年的一个悬而未决的问题，并使动物和人类的DPOAE记录成为可能。其次，考虑到上述情况，我们试图将我们在内耳的研究轴线从听觉系统转移到前庭系统，并最终将其与听觉系统结合起来。 ...更多信息 能够在全细胞膜片钳模式下记录啮齿类动物前庭神经节细胞的动作电位。我们还通过DNA芯片揭示了前庭神经节细胞中毒蕈碱受体mRNA的表达。计划在不久的将来进行的研究：1）我们仍在继续使用基因敲除小鼠和野生型小鼠进行对异常噪声和耳毒性药物敏感性的比较研究。这是因为基因敲除小鼠是独立产生的，结果可能与美国组不同。2）由于表明啮齿动物前庭神经节细胞上存在毒蕈碱受体，我们计划首先研究毒蕈碱受体对神经元兴奋性的调节，然后揭示基因敲除小鼠和野生型小鼠之间神经元放电模式的差异。此外，通过研究离子通道对动作电位形成的贡献的差异，将推断毒蕈碱受体对前庭神经节细胞发育过程的贡献。少

This year, we continued our research on the basis of what we have established during the past two years. However, we encountered two troubles at the beginning of the year. First, because of epidemic problems, supply of the knock-out animals was disconnected for about half a year. The stable supply was re-established in November and we resumed the experiments. Secondly, in the meantime, a competing laboratory in the States reported that their mice lacking muscarinic receptors (product independent of our knock-outs) had almost normal hearing and similar susceptibility to ototoxic agents (Maison SF, et al. 2005).However, we made progress in two points. First, we revised the computer software to record OAEs, which was a pending problem from the last year, and enabled recording DPOAEs in animals as well as in humans. Secondly, considering the situation described above, we tried to shift the axis of our research in the inner ear from the auditory system to the vestibular system and finally w … More ere able to record action potentials of vestibular ganglion cells in rodents on the whole-cell patch clamp mode. We also revealed the expression of mRNAs for muscarinic receptors in vestibular ganglion cells by means of DNA arrays.Planned studies in the near future :1) We still continue the experiments on comparative studies on susceptibility to extraordinary noise and to ototoxic drugs using knock-out and wild-type mice. This is because the results may differ from those from the USA group, since the knock-out mice were independently produced.2) Since the existence of muscarinic receptors on the vestibular ganglion cells in rodents was indicated, we plan first to investigate modulation of excitability of neurons by muscarinic receptors and then to reveal the difference of neuronal firing patterns between knock-out and wild-type mice. Moreover, by investigating the difference in contribution of ionic channels on action potential formation, the contribution of muscarinic receptors to developmental processes of vestibular ganglion cells will be deduced. Less