Studies in cochlear hair cell transduction

哺乳动物的耳朵含有两种感觉感受器细胞：内毛细胞和外毛细胞。 (OHC)。内分泌细胞将听觉信息传递给大脑，而内分泌细胞则充当局部放大器 加大对国际卫生中心的投入。如果没有正常运作的神经细胞，听力阈值会严重下降，选择性 有效地消除了不同的声音频率。内分泌细胞如何促进耳朵的反应是 听力科学的中心问题。有两种相互矛盾的理论。在一种情况下，假设输入 毛细胞的细胞器，即所谓的立体纤毛，是能动的，并将能量反馈给振动系统。 它们被嵌入其中，从而促进了响应。另一种理论是基于观察到的 OHC会根据其电状态的变化而改变其长度。这些长度更改包括 由一种新的分子马达Prestin介导，我们在五年前发现了它。这两种理论都有一些 实验支持，两者都有弱点。本项工作的主要目的是建立 通过OHC的放大模式，从而调和这两种理论，这是实现 这是为了研究转基因小鼠的生理行为，这些小鼠表达突变形式的prestin。在其他 换句话说，我们研究了动物的反应特征，这些动物的毛细胞中有prestin分子，但 分子是无功能的。因此，这些动物没有活动的毛囊，因此， 没有提议的扩增手段，而另一种没有改变。其他实验包括 旨在研究Prestin的分子性质，它可能是哺乳动物听力中的关键分子。 先天或后天的听力损失和耳聋，在我们的年老时尤其普遍 人口，是最常见的公共卫生问题之一。其中非常重要的一部分 缺陷涉及毛细胞的退化或死亡，尤其是毛细胞。我们的全部努力都集中在 揭示了OHC的特性及其在听证过程中的独特作用。

The mammalian ear contains two types of sensory receptor cells, inner hair cells (IHC) and outer hair cells (OHC). IHCs communicate auditory information to the brain, whereas OHCs function as local amplifiers to boost the input to IHCs. Without functioning OHCs, hearing threshold is severely degraded and selectivity to different sound frequencies is effectively eliminated. How OHCs boost the ear's response is one of the central issues of hearing science. There are two competing theories. In one, it is assumed that the input organelles of hair cells, so called stereocilia, are motile and feed energy back to the vibrating system in which they are embedded, thereby boosting the response. The other theory is based on the observation that OHCs change their length in response to changes in their electrical state. These length changes are mediated by a novel molecular motor, prestin, which we identified five years ago. Both theories have some experimental support and both have weaknesses. It is the principal aim of the present work to establish the mode of amplification by OHCs and thereby reconcile the two theories, The primary means of accomplishing this is to study the physiological behavior of mice engineered to express mutated forms of prestin. In other words, we examine response characteristics of animals that have the molecule prestin in their OHCs, but the molecule is non-functional. Thereby, these animals do not have motile OHCs and, consequently, one of the proposed means of amplification is absent, while the other is unaltered. Additional experiments are designed to examine the molecular nature of prestin, which may be the key molecule in mammalian hearing. Hearing loss and deafness, congenital or acquired during life, and especially prevalent in our aging population, represent one of the most common public health problems. A very significant fraction of these deficits involve deterioration or death of hair cells, especially OHCs. Our entire effort is focused on unreveling the properties of OHCs and their unique function in the hearing process.