School of Molecular Bioscience, G08, University of Sydney, New South Wales 2006, Australia.
J Inorg Biochem. 2012 Oct;115:211-9. doi: 10.1016/j.jinorgbio.2012.03.009. Epub 2012 Apr 21.
The change in the NMR chemical shift of (23)Na(+) induced by the shift reagent TmDOTP was examined under various experimental conditions typical of cells, including changed Na(+), K(+), PO(4)(3-), and Ca(2+) concentrations, pH and temperature. A mathematical model was developed relating these factors to the observed chemical shift change relative to a capillary-sphere reference. This enabled cation concentrations to be deduced quantitatively from experimental chemical shifts, including those observed during biological time courses with cell suspensions containing TmDOTP DOTP, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylenephosphonate) [corrected]. The model was applied to a (23)Na NMR time course in which monensin, a sodium ionophore, was introduced to human erythrocytes, changing the concentration of cations which may bind TmDOTP, and also resulting in cell volume changes. Using the model with experimentally determined conditions, the chemical shift was predicted and closely followed the experimental values over time. In addition to the model, parameter fitting was achieved by calculating the likelihood distribution of parameters, and seeking the maximum likelihood with a Bayesian type of analysis.
在各种典型细胞实验条件下，研究了（23）Na（+）的 NMR 化学位移变化（23）Na（+）受位移试剂 TmDOTP 的影响。建立了一个数学模型，将这些因素与相对于毛细管球参考观察到的化学位移变化相关联。这使得可以从实验化学位移中定量推断出阳离子浓度，包括在含有 TmDOTP、DOTP、1,4,7,10-四氮杂环十二烷-1,4,7,10-四（亚甲基膦酸酯）[已更正]的细胞悬浮液中进行生物时间过程时观察到的那些。该模型应用于（23）Na NMR 时间过程，其中莫能菌素，一种钠离子载体，被引入人红细胞，改变可能与 TmDOTP 结合的阳离子浓度，并且还导致细胞体积变化。使用实验确定条件的模型，预测了化学位移，并随着时间的推移密切跟踪实验值。除了模型，还通过计算参数的似然分布并通过贝叶斯类型的分析寻求最大似然来实现参数拟合。
