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: 7303698
• 负责人: Nicholas A Delamere
• 金额: $ 25.12万
• 依托单位: UNIVERSITY OF ARIZONA
• 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/7303698
• 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）：拟研究Na， k - atp酶在视神经头星形胶质细胞中的作用。星形胶质细胞在神经元微环境中调节pH、钾、钙和谷氨酸的能力与Na， k - atp酶有关。星形胶质细胞表达两种Na， k - atp酶亚型alpha1和alpha2。这两种异构体似乎具有不同的功能，但我们对它们各自的作用或对星形细胞生理学的影响还没有完整的信息。Na， k - atp酶α 1具有重要的家政功能，调节细胞质钠的全细胞浓度。我们对Na， k - atp酶α 2亚型特别感兴趣，因为初步研究表明它具有不同的作用。事实并非如此