Cochlear and vestibular ion transport

耳蜗和前庭离子传输

• 批准号: 7252556
• 负责人: DANIEL C MARCUS
• 金额: $ 36.03万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252556
• 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; Condition; 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; Membrane; Meniere' 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; adrenergic; base; calbindin; cell type; epithelial Na+ channel; genetic regulatory protein; interest; knock-down; novel; programs; response; solute; water channel

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）：Meniere氏病是由耳蜗和前庭迷宫的内淋巴水滴特征的病理实体之一。水力可以是由与内淋巴系统接触的上皮细胞的离子转运性能改变产生的。关于涉及的病理过程的细胞基础知之甚少，因为从正常和病理系统中缺乏有关离子分泌和吸收机制的数据。内晶的独特之处在于它是体内唯一具有高钾（K+）浓度和低钠（Na+）和钙（Ca2+）浓度的细胞外液，这是维持正常听力和平衡至关重要的组合物。在该奖项的前期，我们对内耳运输过程的理解大大增加了。然而，在前庭迷宫中的耳蜗和半圆形管道（SCCD）中的两个上皮区域，Reissner的膜（RM），为内淋巴液液体组成和体积的稳态做出了重要贡献，但是我们对它们功能的理解落后于其他细胞类型的功能。提议研究负责由RM和SCCD在前庭迷宫中的离子K+，Na+，Ci-，HC03-，Ca2+和水的运输过程。这些研究将利用我们已建立的微分解，电生理学，分子生物学和免疫组织化学技术以及这些研究的新颖扩展（耳蜗切片的准备以更好地保留隔离组织的详细组织功能，在电导过程中，以研究偏细胞传输路径的特定性能，并确定降落层的表达性能，并确定降落性的倾向分析。基因）。实验设计将测试有关RM和SCCD运输的一系列假设，这些假设将导致对这些上皮的基本关键作用的理解在听力和平衡的健康和疾病中。