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ION CHANNELS AND DEVELOPMENT OF HAIR CELLS

离子通道和毛细胞的发育

基本信息

批准号：
6516058
负责人：
ALBERT JAMES HUDSPETH
金额：
$ 20.24万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 2003-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6516058
关键词：
animal genetic material tag biological signal transduction calcium channel chick embryo chickens complementary DNA developmental genetics developmental neurobiology ear hair cell gene induction /repression mechanoreceptors molecular cloning neurogenesis neurogenetics nucleic acid sequence potassium channel protein structure function voltage gated channel

项目摘要

DESCRIPTION: Stimulation of the internal ear by a sound or an acceleration evokes an electrical response in hair cells, the ear's sensory receptors. In many auditory organs , each hair cell's response is highly sensitive to the frequency of stimulation as a result of electrical tuning mediated by ion channels in the cell's membrane. Ion channels are also involved in the release of synaptic transmitter that excites nerve fibers, which in turn, carry information into the brain. The prominence of ion channels in both signalling processes motivates the proposed investigations of the structures and function of such channels in hair cells. Hair cells are highly specialized cells endowed with unique organelles for the capture of stimulus energy and for the control of synaptic transmitter release. Unfortunately, the small number of hair cells in an ear greatly impedes the study of the proteins that constitute these organelles and account for their unique properties. Making use of the tools of molecular biology, the proposed experiments involve the identification of genes uniquely expressed in hair cells, as well as those active only in supporting cells. This approach should provide a better understanding of the proteins that account for the hair cell's specialized properties. Hair cells of the human internal ear are damaged by numerous genetic conditions, infections, loud sounds, ototoxic drugs, and aging. Until recently, there was no evidence that the receptor cells lost as a result of such processes could be replaced. During the past decade, however, several research groups have demonstrated hair cell regeneration in the ears of birds and even mammals. The proposed studies of early stages in the internal ear's development should indicate which chemical factors are of importance in the decision to create new hair cells and in each hair cell's maturation. More specifically, crucial chemical messengers will be identified by use of viruses to interfere with their normal functions. Hair cells are probably maintained by exposure to growth factors supplied by other cell types. Similar techniques will additionally show which factors are of particular importance in this context. These studies should provide information useful in promoting the survival, repair, and eventual replacement of hair cells in the human internal ear.

描述：声音或加速对内耳的刺激在毛细胞中引起电反应，毛细胞是耳朵的感官受体。在许多听觉器官中，每个毛细胞的反应对由于电调谐而产生的刺激频率由细胞膜上的离子通道。离子通道也参与了释放突触递质，刺激神经纤维，进而，将信息带入大脑。离子通道在两者中的重要性信号传递过程推动了对结构的拟议调查以及毛细胞中这种通道的功能。毛细胞高度具有捕捉刺激的独特细胞器的特化细胞能量和控制突触递质的释放。不幸的是，耳朵中的少量毛细胞极大地阻碍了对构成这些细胞器的蛋白质，并解释了它们独特的属性。利用分子生物学的工具，提出了实验涉及鉴定在头发中唯一表达的基因。细胞，以及那些仅在支持细胞中活动的细胞。这种方法应该能让我们更好地理解导致毛细胞的特殊属性。人类内耳的毛细胞受到许多基因的破坏疾病、感染、响亮的声音、耳毒性药物和衰老。直到最近，没有证据表明受体细胞的损失是由于这样的流程是可以被取代的。然而，在过去的十年里，有几个研究小组已经证明了耳部毛细胞的再生。鸟类，甚至哺乳动物。建议进行的早期阶段研究内耳的发育应该表明哪些化学因素是在决定创造新的毛细胞和每个毛细胞的成熟。更具体地说，关键的化学信使将是通过使用病毒干扰其正常功能来识别。头发细胞可能是通过暴露于由其他细胞类型。类似的技术还将显示哪些因素在这方面具有特别重要的意义。这些研究应该提供有助于促进人类生存、修复和最终生存的信息替换人类内耳中的毛细胞。