Sensory Processing in Mammalian Vestibular Organs

描述：(申请人提供) 前庭器官中的感觉毛细胞提供有关头部的信息 控制眼睛、头部和身体位置的反射动作。损坏这些东西 由于年龄、疾病或创伤而导致的细胞活动能力受损， 生活质量。这项建议侧重于各阶层的贡献。 离子通道蛋白对哺乳动物毛细胞正常功能的影响 前庭器官。三个具体目标中的每一个都指向不同的阶段 刺激加工：机械电转导，感受器的形成 通过电压门控离子通道和传入传递的电位1。结果 将检查毛细胞类型的变异(I与II)，毛细胞 感觉上皮内的位置，以及发育阶段。 机械电传导是毛束偏转的过程 门机械敏感的离子通道，产生转换电流。它有 是在体外条件下测量的，这些条件可能已经改变了它的 属性。一系列实验将使记录条件 生理上的。毛束形态对信号转导和信号转导的影响 束状硬度知之甚少，我们将对其进行检验。 转换电流引发电压变化(感受器电位)，这 激活电压门控离子通道。钾(K+)通道帮助设置休息 并提供感受器电位的负反馈。补语 毛细胞中K+通道的数目随细胞类型和感觉位置的不同而不同 上皮组织。单个毛细胞表达的K+通道亚基将是 表达谱鉴定：从单细胞中扩增出的RNA 被用来探测一组候选的DNA。候选亚单位将是 随后进行免疫细胞化学以定位该蛋白。电压门控 哺乳动物前庭毛细胞钠电导(GNA)在非常短的时间内失活 负电位，引发了对其功能的质疑。机械学 控制失活范围，GNA对受体电位的影响， 并将对GNA蛋白的身份进行调查。 传入神经元在I型毛细胞上形成大的杯状(花萼)末端，在 与它们在其他毛细胞上形成的小末端形成对比。传入 因此，I型毛细胞的传播很可能是不寻常的 属性。其中一组实验将描述突触小泡胞吐作用： I型毛细胞与II型毛细胞有区别吗？尽其所能 哺乳动物前庭毛细胞与耳蜗毛细胞的特性不同 毛细胞？另一组将测试类型I特定电导是否， GK，L，被突触间隙中的传入递质抑制。 这种抑制会对传入产生强烈的正反馈 变速箱。突触后花盏末端的离子通道，它启动 毛细胞递质的传入反应(S)，将被描述。

DESCRIPTION: (provided by applicant) The sensory hair cells in vestibular organs provide information about head movements to reflexes that control eye, head and body position. Damage to these cells as a result of age, disease or trauma leads to impaired mobility and quality of life. This proposal focuses on the contributions of various classes of ion channel protein to the normal function of hair cells in mammalian vestibular organs. Each of three specific aims is directed at a different stage in stimulus processing: mechanoelectrical transduction, shaping of the receptor potentia1 by voltage-gated ion channels, and afferent transmission. Results will be examined for variation with hair cell type (I vs. II), hair cell location within the sensory epithelium, and developmental stage. Mechanoelectrical transduction is the process by which hair bundle deflection gates mechanosensitive ion channels, producing a transduction current. It has been measured under in vitro conditions that are likely to have changed its properties. One series of experiments will make recording conditions more physiological. The influence of hair bundle morphology on transduction and bundle stiffness is poorly understood and will be examined. The transduction current initiates a voltage change (receptor potential), which activates voltage-gated ion channels. Potassium (K+) channels help set resting potential and provide negative feedback on receptor potentials. The complement of K+ channels in a hair cell varies with cell type and location in the sensory epithelium. K+ channel subunits expressed by single hair cells will be identified by expression profiling: RNA amplified from cDNA from single cells is used to probe a panel of candidate cDNAs. Candidate subunits will be followed up with immunocytochemistry to localize the protein. The voltage-gated sodium conductance (gNa) in mammalian vestibular hair cells inactivates at very negative potentials, raising questions about its function. Mechanisrns controlling the inactivahon range, the effect of gNa on the receptor potential, and the identity of the gNa protein will be investigated. Afferent neurons make large cup-shaped (calyx) endings on type I hair cells, in contrast to the small (bouton) endings they form on other hair cells. Afferent transmission from type I hair cells is therefore likely to have unusual properties. One set of experiments will describe synaptic vesicle exocytosis: Is it different in type I hair cells relative to type II hair cells? Do its properties in mammalian vestibular hair cells differ from those in cochlear hair cells? Another set will test whether the type-I-specific conductance, gK,L, is inhibited by the afferent transmitter present in the synaptic cleft. Such inhibition would produce strong positive feedback on afferent transmission. Ion channels in the postsynaptic calyx ending, which initiate the afferent response to the hair cell transmitter(s), will be characterized.