Liu Huizhan, Li Yi, Chen Lei, Zhang Qian, Pan Ning, Nichols David H, Zhang Weiping J, Fritzsch Bernd, He David Z Z
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
Department of Otorhinolaryngology, Beijing Tongren Hospital, Beijing Capital Medical University, Beijing, China.
PLoS One. 2016 Dec 28;11(12):e0168953. doi: 10.1371/journal.pone.0168953. eCollection 2016.
Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.
耳蜗毛细胞和血管纹对正常听力至关重要。毛细胞将机械刺激转化为电信号，而血管纹负责产生内淋巴电位（EP），这是毛细胞机械转导的驱动力。我们通过使用两种小鼠模型来探究毛细胞和血管纹是否相互依赖以维持生存。Atoh1条件性敲除小鼠在出生后四周内会失去所有毛细胞，用其来确定毛细胞的缺失是否会影响血管纹的功能和存活。我们发现，尽管所有毛细胞完全缺失，但血管纹的形态和EP在很长一段时间内仍保持正常。然后，我们使用一种由于Mitf基因突变而具有异常血管纹形态和功能的小鼠模型，来确定在没有正常内淋巴电化学环境的情况下，毛细胞是否能够存活并转导声音信号。血管纹缺陷表现为血管纹中间细胞缺失和EP降低，导致出生后第18天之后从基底到顶端的系统性外毛细胞死亡。然而，18 mV的EP足以维持外毛细胞的存活。令人惊讶的是，内毛细胞的存活对外淋巴电位降低的敏感性较低。我们的研究表明，血管纹的正常功能对于成年外毛细胞的存活至关重要，而血管纹的存活和正常功能并不依赖于功能性毛细胞。
