Cochlear and vestibular ion transport

耳蜗和前庭离子传输

基本信息

批准号：
7626786
负责人：
DANIEL C MARCUS
金额：
$ 37.72万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7626786
关键词：
ATP phosphohydrolase Adrenal Cortex Hormones Adrenergic Agents Adrenergic beta-Agonists Anions Area Award Bathing Bicarbonates Binding Calcium Carrier Proteins Cations Cell Line Cells Clinical Cochlea Cochlear duct Communities Complement component C1s Cyclic AMP Cyclic AMP-Dependent Protein Kinases Cystic Fibrosis Transmembrane Conductance Regulator Data Development Duct (organ) structure Ductal Epithelium Ear Edema Endocrine system Endolymph Endolymphatic Hydrops Epithelial Epithelial Cells Epithelial Physiology Epithelium Equilibrium Experimental Designs Extracellular Fluid Genes Glucocorticoids Health Hearing Hearing problem Homeostasis Hormonal Investigation Ion Channel Ion Transport Ion Transport Alteration Ions Labyrinth Lead Link Liquid substance Mediating Meniere&apos s Disease Messenger RNA Methods Microdissection Molecular Organ Pathologic Processes Pathway interactions Perilymph Phosphorylation Physiological Positioning Attribute Potassium Preparation Process Property Proteins RNA Regulation Research Personnel Role Route Scanning Semicircular canal structure Sensory Series Signal Pathway Signal Transduction Slice Sodium Stereocilium Surface System Techniques Testing Tissues Transcript Transport Process Vestibular Labyrinth Vestibular membrane Water absorption active control adrenergic base calbindin cell type epithelial Na+ channel genetic regulatory protein interest knock-down novel programs response solute water channel

项目摘要

DESCRIPTION (provided by applicant): Meniere's Disease is one of the pathological entities characterized by endolymphatic hydrops of the cochlear and vestibular labyrinths. Hydrops can result from an alteration of ion transport properties of the epithelial cells bordering the endolymphatic system. Little is known about the cellular basis of the pathologic processes involved because data are lacking from normal as well as pathological systems concerning mechanisms of secretion and absorption of ions. Endolymph is unique in that it is the only extracellular fluid in the body with a high potassium (K+) concentration and low sodium (Na+) and calcium (Ca2+) concentrations, a composition that is essential to sustain normal hearing and balance. Our understanding of transport processes in the inner ear has increased enormously over the previous periods of this award. However, two epithelial regions, Reissner's membrane (RM) in the cochlea and the semicircular canal ducts (SCCD) in the vestibular labyrinth, make important contributions to the homeostasis of endolymphatic fluid composition and volume, but our understanding of their functions lags behind that of other cell types in the ear. It is proposed to study the transport processes responsible for fluxes of the ions K+, Na+, CI-, HC03-, Ca2+ and water in the vestibular labyrinth and cochlea by RM and SCCD. These investigations will utilize our established microdissection, electrophysiologic, molecular biologic and immunohistochemical techniques as well as novel extensions of these (cochlear slice preparation to better preserve function of delicate tissues during isolation, conductance scanning to study paracellular transport pathways, fluctuation analysis of epithelial currents to determine ion channel properties and RNA inhibition to knock down the expression of specific genes). The experimental design will test a series of hypotheses about RM and SCCD transport that will lead to an understanding of fundamental, key roles of these epithelia in the health and disease of hearing and balance.

描述（由申请人提供）：梅尼埃病是一种以耳蜗和前庭迷路内淋巴积水为特征的病理实体。水肿可能是由于内淋巴系统边缘上皮细胞的离子传输特性改变所致。由于缺乏有关离子分泌和吸收机制的正常和病理系统的数据，因此对所涉及的病理过程的细胞基础知之甚少。内淋巴的独特之处在于，它是体内唯一一种钾 (K+) 浓度高、钠 (Na+) 和钙 (Ca2+) 浓度低的细胞外液，而钠 (Na+) 和钙 (Ca2+) 浓度对于维持正常听力和平衡至关重要。与该奖项的前几个时期相比，我们对内耳传输过程的了解有了极大的提高。然而，两个上皮区域，耳蜗中的赖斯纳膜（RM）和前庭迷路中的半规管（SCCD），对内淋巴液成分和体积的稳态做出了重要贡献，但我们对它们功能的理解落后于内淋巴液的功能。耳朵中的其他细胞类型。建议通过 RM 和 SCCD 研究前庭迷路和耳蜗中 K+、Na+、CI-、HC03-、Ca2+ 和水离子通量的传输过程。这些研究将利用我们已建立的显微解剖、电生理学、分子生物学和免疫组织化学技术以及这些技术的新扩展（耳蜗切片制备以在分离过程中更好地保护脆弱组织的功能，电导扫描以研究旁细胞运输途径，上皮电流的波动分析以确保确定离子通道特性和 RNA 抑制以降低特定基因的表达）。实验设计将测试一系列关于 RM 和 SCCD 运输的假设，这些假设将有助于了解这些上皮细胞在健康以及听力和平衡疾病中的基本、关键作用。