ELECTRONEUTRAL AND SLOW-RATE TRANSPORTERS

电中性和慢速传输器

• 批准号: 7598497
• 负责人: MARK A MESSERLI
• 金额: $ 3.52万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598497
• 关键词: ATP-Binding Cassette Transporters; Biological Assay; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Institution; Ions; Kinetics; Measures; Monitor; Multi-Drug Resistance; Rate; Research; Research Personnel; Resources; Source; System; Time; United States National Institutes of Health; density; extracellular; sensor; voltage clamp

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The study of electroneutral and slow rate transporters has lagged behind the study of electrogenic transporters due to the difficulty in monitoring transport rates. Voltage clamp is used to measure currents that are proportional to transport rates in systems with a high density of electrogenic transporters that have high transport rates. This is a real-time assay for monitoring transport kinetics. Electroneutral transporters, however, do not generate current at all while slow-rate transporters generate current that is not detectable unless transporter density reaches 1-10 thousand times greater than that used with high rate electrogenic transporters. We have found that a sensitive, real-time assay for monitoring transport exists by using extracellular, electrochemical sensors to monitor gradients established during transport. By monitoring two points in the concentration gradient we can calculate flux of the analyte that is proportional to transport rate. We are exploring two separate groups of transporters in this manner, the multidrug resistance (MDR) transporters of the ATP-binding cassette (ABC) superfamily and electroneutral ion transporters, specifically the nongastric H+/K+ transporter.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 由于难以监测运输速率，因此对电荷和慢速转运蛋白的研究落后于对电源转运蛋白的研究。 电压夹用于测量与具有较高传输速率的高密度的电源转运蛋白密度的系统中的运输速率成正比的电流。 这是监测运输动力学的实时测定。 但是，除非转运蛋白密度比高速电源转运蛋白所用的转运蛋白密度达到1-10千倍，否则电荷转运蛋白根本不会产生电流，而缓慢速率转运蛋白会产生无法检测到的电流。 我们发现，通过使用细胞外电化学传感器监测运输过程中建立的梯度来监测运输的敏感实时测定。 通过监视浓度梯度中的两个点，我们可以计算与运输速率成正比的分析物的通量。 我们正在以这种方式探索两个单独的转运蛋白组，即ATP结合盒（ABC）超家族和电反离离子转运蛋白的多药电阻（MDR）转运蛋白，特别是nongastric H+/K+转运蛋白。