Studies in cochlear hair cell transduction

哺乳动物的耳朵包含两种类型的感觉感受器细胞，内毛细胞（IHC）和外毛细胞 （OHC）。IHC将听觉信息传递给大脑，而OHC则充当局部放大器， 加大对IHC的投入。如果没有正常的OHC，听力阈值会严重下降， 有效地消除了不同的声音频率。OHC如何增强耳朵的反应是其中一个 听觉科学的核心问题。有两种相互竞争的理论。在一种情况下，假设输入 毛细胞的细胞器，所谓的静纤毛，是能动的，并将能量反馈给振动系统， 它们被嵌入其中，从而增强响应。另一种理论是基于观察， OHC响应于其电状态的变化而改变其长度。这些长度变化是 由一种新的分子发动机，普雷斯廷介导，这是我们五年前发现的。这两种理论都有一些 实验支持和两者都有弱点。本工作的主要目的是建立 OHC的放大模式，从而调和两种理论，实现的主要手段 这是为了研究经工程改造以表达普雷斯廷突变形式的小鼠的生理行为。换句 换句话说，我们研究了在OHC中含有普雷斯廷分子的动物的反应特征，但是 分子是非功能性的。因此，这些动物没有能动的OHC，因此， 一种拟议的放大手段不存在，而另一种则未改变。其他实验包括 旨在研究普雷斯廷的分子性质，它可能是哺乳动物听力的关键分子。 听力损失和耳聋，先天性或后天在生活中，尤其是在我们的老龄化普遍 人口，是最常见的公共卫生问题之一。其中很大一部分 缺陷涉及毛细胞，特别是OHC的退化或死亡。我们所有的努力都集中在 揭示了OHC的性质及其在听证过程中的独特功能。

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.