MULTIPLE QUANTUM NMR STUDIES OF SODIUM AND POTASSIUM IN THE RAT BRAIN

大鼠脑中钠和钾的多重量子核磁共振研究

• 批准号: 3789491
• 负责人: A C MCLAUGHLIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3789491
• 关键词: bioenergetics; brain metabolism; cats; heart metabolism; ion transport; ischemia; laboratory rat; liver metabolism; membrane permeability; nuclear magnetic resonance spectroscopy; perfusion; potassium; quantum chemistry; sodium

We have developed a noninvasive technique for studying transmembrane ion gradients in various tissues. For nuclei such as 23Na and 39K, a multiple quantum NMR approach can select populations of ions which exhibit biexponential relaxation. This type of relaxation occurs for ions which associate with macromolecules. Our goal is to apply this technique clinically to study tissue pathology. First, we need to establish that this technique can be used to selectively monitor intracellular ions. Initially, double quantum filtered (DQF) 23Na and 39K NMR spectra were obtained from rat brain in vivo. Upon death, the DQF 23Na signal increased 3-fold, consistent with the well-known influx of sodium ions into the cell. This technique could distinguish sodium ions from at least two different compartments in the brain. Studies in the cat brain following death, established a temporal correlation between the increase in triple quantum filtered 23Na signal and the decrease in ATP levels (by 31P NMR). To test the hypothesis that the multiple quantum NMR approach can monitor intracellular sodium, two approaches were used. First in rat brain, the time course for the increase in DQF 23Na signal following death correlated with the time course for the decrease in extracellular sodium measured by ion-sensitive surface electrodes. The second approach utilized the perfused organs, liver and heart, which unlike the intact brain, can be successfully treated with shift reagents. Using shift reagents, DQF 23Na signals were separated into intracellular and extracellular components. In the liver, little signal was shifted, indicating that most of the DQF 23Na signal in the absence of shift reagent was due to intracellular sodium. Following ischemia, the time course for the increase in DQF 23Na signal (without reagent) correlated with the increase in intracellular sodium as measured by conventional 23Na NMR with shift reagent.

我们发展了一种非侵入性的跨膜离子研究技术 各种组织中的梯度。 对于像23 Na和39 K这样的原子核， 量子NMR方法可以选择离子的群体， 双指数松弛 这种类型的弛豫发生在 与大分子结合。 我们的目标是应用这项技术 临床上研究组织病理学。 首先，我们需要确定 该技术可用于选择性地监测细胞内离子。 最初，使用双量子滤波（DQF）23Na和39K NMR谱， 从体内的大鼠脑中获得。 死亡后，DQF 23 Na信号 增加了3倍，与众所周知的钠离子流入一致 进入细胞。 这项技术可以区分钠离子， 大脑中两个不同的区域 对猫脑的研究 在死亡后，建立了一个时间相关性的增加， 在三重量子过滤的23 Na信号和ATP水平的降低（通过 31P NMR）。 为了验证多量子核磁共振方法 可以监测细胞内钠，使用两种方法。 大鼠中首次 脑，DQF 23 Na信号增加的时间过程， 死亡与细胞外基质减少的时间进程相关， 用离子敏感表面电极测量钠。 第二种方法 利用灌注的器官，肝脏和心脏，这与完整的 大脑，可以成功地治疗转移试剂。 使用shift 试剂，DQF 23 Na信号被分离到细胞内， 细胞外成分 在肝脏，几乎没有信号转移， 表明大多数DQF 23 Na信号在没有移位的情况下 试剂是由于细胞内钠。 缺血后， DQF 23 Na信号（无试剂）增加的过程相关 随着细胞内钠的增加，如通过常规23 Na 用位移试剂进行NMR。