Na,K-ATPase studies on optic nerve head astrocytes

Na,K-ATP酶对视神经乳头星形胶质细胞的研究

• 批准号: 6949904
• 负责人: Nicholas A Delamere
• 金额: $ 25.73万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949904
• 关键词: animal tissue; astrocytes; biological signal transduction; biological transport; calcium; cell growth regulation; disease /disorder model; gene expression; genetic regulation; glaucoma; glutamates; hydrogen transport; laboratory rat; molecular pathology; neurogenetics; neuroregulation; nitric oxide synthase; optic nerve; potassium; protein isoforms; protein structure function; sodium potassium exchanging ATPase

DESCRIPTION (provided by applicant): Studies are proposed on Na, K-ATPase in optic nerve head astrocytes. The ability of astrocytes to regulate pH, potassium, calcium and glutamate in the neuronal microenvironment is linked to Na, K-ATPase. Astrocytes express two Na,K-ATPase isoforms alpha1 and alpha2. The two isoforms appears to have different functions but we do not have complete information on their respective roles or the implications for astrocyte physiology. Na,K-ATPase alpha1 has a vital housekeeping function, regulating the cell-wide concentration of cytoplasmic sodium. We are particularly interested in the Na,K-ATPase alpha2 isoform because Preliminary Studies suggest it has a different role. It does not appear control cell-wide sodium concentration but instead we think Na,K-ATPase alpha2 may be specialized in a way that causes it to have a major influence on glutamate uptake, cell calcium balance and possibly cell growth. Experiments are proposed to study how and astrocytes has the potential to impair the ability of the cell to accumulate extracellular potassium, transport glutamate and protons and regulate cytoplasmic calcium. We also propose studies to examine the potential impairment of Na,K-ATPase function by in vitro episodes of ATP depletion and nitric oxide exposure and by elevated intracellular pressure in vivo. The aims are: (AIM 1) Determine the influence of Na, K-ATPase alpha2 activity on glutamate uptake; (AIM 2) Determine how altered Na,K-ATPase alpha2 activity leads to changes in cytoplasmic calcium stores and subsequent changes in astrocyte behavior; (AIM 3) Study how abnormal Na,K-ATPase activity could impact proton transport mechanisms; (AIM 4) Study the factors that cause abnormal Na,K-ATPase function or expression.

描述(申请人提供)：建议对视神经头星形胶质细胞中的Na，K-ATPase进行研究。星形胶质细胞调节神经元微环境中的pH、钾、钙和谷氨酸的能力与Na，K-ATPase有关。星形胶质细胞表达两种Na，K-ATPase亚型：α1和α2。这两种异构体似乎具有不同的功能，但我们并不完全了解它们各自的作用或对星形胶质细胞生理学的影响。Na，K-ATPaseα1具有重要的内务功能，调节整个细胞内细胞质钠的浓度。我们对Na，K-ATPaseα2亚型特别感兴趣，因为初步研究表明它有不同的作用。它不会 似乎控制着整个细胞的钠浓度，但我们认为Na，K-ATPaseα2可能以某种方式专门化，使其对谷氨酸摄取、细胞钙平衡以及可能的细胞生长产生重大影响。建议进行实验，以研究星形胶质细胞如何潜在地损害细胞积累细胞外钾、运输谷氨酸和质子以及调节细胞质钙的能力。我们还建议进行研究，以检验在体外ATP耗竭和一氧化氮暴露以及体内细胞内压力升高对Na，K-ATPase功能的潜在损害。其目的是：(目的1)确定Na，K-ATPaseα2活性对谷氨酸摄取的影响；(AIM 2)确定Na，K-ATPaseα2活性改变如何导致细胞质钙储存的变化以及随后星形胶质细胞行为的改变；(AIM 3)研究Na，K-ATPase活性异常如何影响质子转运机制；(AIM 4)研究导致Na，K-ATPase功能或表达异常的因素。