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

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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