Functional Astrocyte Leak Potassium Channels

功能性星形胶质细胞渗漏钾通道

• 批准号: 0641828
• 负责人: Min Zhou
• 金额: --
• 依托单位: Ordway Research Institute, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0641828&HistoricalAwards=false
• 关键词: Functional; Astrocyte; Leak; Potassium; Channels

Astrocytes are star-shaped cells that have long been functionally considered to provide structural, housekeeping and metabolic support to neurons in the central nervous system (CNS). This supposition has been based on the fact that astrocytes are not able to relay signals by means of electric impulses, as do neurons. However, astrocytes do exhibit membrane currents that are carried through poorly characterized potassium channels. Although these currents were discovered over 40 years ago, the nature of these channels remains largely unknown. This proposal is focused on determining whether astrocyte currents are carried through a a newly discovery potassium channel family, called two-pore domain potassium channels (2PKs). This project will further explore how changes in astrocyte 2PKs could modulate astrocyte homeostatic functions with consequent effect on neuronal function. Membrane ion channel currents from astrocytes will be measured in acute rat hippocampal slices measure. Potential astrocyte 2PKs will be further explored at the gene level by using single cell RT-PCR, and at the protein level by specific antibody labeling to post astrocytes using confocal immunocytochemistry. The functional impact of astrocytic 2PKs will be determined by silencing identified 2PKs using RNAi in the organotypic cultured hippocampus. These experiments will delineate the role of these channels and clarify the function of astrocytes in general. Since astrocytes play integral roles response of the nervous system to injury or disease, such knowledge has implications for human health as well as for the fundamental understanding of the nervous system. The PI will provide opportunities for undergraduate, graduate, and postdoctoral students to participate in research on astrocytes. The broader impacts were judged as strong, particularly considering the PI is in an institute without ready access to undergraduate students.

星形细胞是一种星形细胞，长期以来一直被认为是为中枢神经系统(CNS)中的神经元提供结构、管家和代谢支持的细胞。这一假设是基于这样一个事实，即星形胶质细胞不能像神经元那样通过电脉冲传递信号。然而，星形胶质细胞确实表现出通过特征不佳的钾通道携带的膜电流。虽然这些洋流是在40多年前发现的，但这些通道的性质在很大程度上仍不清楚。这一建议的重点是确定星形胶质细胞电流是否通过一个新发现的钾通道家族进行，称为双孔区域钾通道(2PKs)。该项目将进一步探讨星形胶质细胞2PKs的变化如何调节星形胶质细胞的稳态功能，从而对神经元功能产生影响。将星形胶质细胞膜离子通道电流测量在急性大鼠海马片上。利用单细胞RT-PCR技术在基因水平上进一步挖掘星形胶质细胞2PKs的潜能，用免疫细胞共聚焦技术对后星形胶质细胞进行特异性抗体标记，在蛋白水平上进一步挖掘星形胶质细胞2PKs的潜能。星形细胞2PKs的功能影响将通过使用RNAi沉默器官型培养的海马区中已鉴定的2PKs来确定。这些实验将描绘出这些通道的作用，并阐明星形胶质细胞的总体功能。由于星形胶质细胞在神经系统对损伤或疾病的反应中发挥着不可或缺的作用，因此这种知识对人类健康以及对神经系统的基本理解都有意义。PI将为本科生、研究生和博士后提供参与星形胶质细胞研究的机会。更广泛的影响被认为是强大的，特别是考虑到PI所在的学院没有随时接触到本科生。