Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Exp Physiol. 2012 Apr;97(4):438-51. doi: 10.1113/expphysiol.2011.059303. Epub 2011 Dec 5.
Hair cells in the mammalian inner ear convert sound into electrical signals that are relayed to the nervous system by the chemical neurotransmitter glutamate. Electrical information encoding sound is then passed through the central nervous system to the higher auditory centres in the brain, where it is used to construct a temporally and spatially accurate representation of the auditory landscape. To achieve this, hair cells must encode fundamental properties of sound stimuli at extremely high rates, not only during mechano-electrical transduction, which occurs in the hair bundles at the cell apex, but also during electrochemical transduction at the specialized ribbon synapses at the cell base. How is the development of such a sophisticated cell regulated? More specifically, to what extent does physiological activity contribute to the progression of the intrinsic genetic programmes that drive cell differentiation? Hair cell differentiation takes about 3 weeks in most rodents, from terminal mitosis during embryonic development to the onset of hearing around 2 weeks after birth. Until recent years, most of the molecules involved in hair cell development and function were unknown, which was mainly due to difficulties in working with the mammalian cochlea and the very small number of hair cells, about 16,000 in humans, present in the auditory organ. Recent advances in the ability to record from the acutely isolated cochlea maintained in near-physiological conditions, combined with the use of genetically modified mouse models, has allowed the identification of several proteins and molecular mechanisms that are crucial for the maturation and function of hair cells. In this article, I highlight recent findings from my laboratory that have furthered our understanding of how developing hair cells acquire the remarkable sensitivity of adult auditory sensory receptors.
哺乳动物内耳中的毛细胞将声音转化为电信号,这些电信号通过化学递质谷氨酸传递到神经系统。然后,声音的电信息编码通过中枢神经系统传递到大脑中的高级听觉中枢,在那里它被用来构建听觉景观的时间和空间准确表示。为了实现这一点,毛细胞必须以极高的速率对声音刺激的基本属性进行编码,不仅在发生在细胞顶端毛束中的机械 - 电转导过程中,而且在细胞基部的专门带状突触中的电化学转导过程中也是如此。这种复杂细胞的发育是如何调控的?更具体地说,生理活动在多大程度上促进了驱动细胞分化的内在遗传程序的进展?在大多数啮齿动物中,毛细胞的分化大约需要 3 周时间,从胚胎发育过程中的终末有丝分裂到出生后大约 2 周开始听力。直到最近几年,大多数参与毛细胞发育和功能的分子仍然未知,这主要是由于难以研究哺乳动物耳蜗和听觉器官中存在的非常少量的毛细胞(人类约为 16000 个)所致。近年来,在接近生理条件下对急性分离的耳蜗进行记录的能力的进步,结合使用基因修饰的小鼠模型,已经允许鉴定出几种对于毛细胞的成熟和功能至关重要的蛋白质和分子机制。在本文中,我强调了我实验室的最新发现,这些发现进一步加深了我们对发育中的毛细胞如何获得成年听觉感觉受体的惊人敏感性的理解。