NMR STUDIES OF METAL IONS IN INTACT CELLS AND TISSUES

我们研究的一个主要目标是了解可能的调节作用

A primary goal of our research is to understand possible regulatory role of metal ions (Na+, K+, Mg2+ & Ca2+) in cellular proliferation, differentiation, and in hormonal regulation of various cellular processes. We seek also to understand how the concentrations of intracellular ions are managed by various membrane transport processes, and how such regulation goes astray in disorders such as cancer, diabetes, sickle cell disease and in hypertension, including that due to lead toxicity. Our research tool is NMR spectroscopy. Cells and tissues to be used in our research include human blood cells, rat kidney and heart cells, intact rat heart and kidney, and surgical specimens of non-neoplastic and neoplastic human tissue. Specific aims to be pursued are: (1) To examine if the mitogenic stimulation of lymphocyte proliferation in vitro is accompanied by an increase in Na+ permeability of the plasma membrane; (2) To investigate the effects of diabetes mellitus upon intracellular Na+, free Ca2+ and pH, in rat heart and kidney tissue; (3) To establish that an alteration in NMR- visible Na+ occurs in the neoplastic tissue in comparison to non-neoplastic tissue and to determine if benign and malignant fors of neoplasia can be distinguished on the basis of their intracellular Na+ concentration: (4) To test the hypothesis that a decrease in intracellular free Mg2+ and pH, along with an increase in NMR visibile intracellular Na+ and free Ca2+, is associated with essential hypertension; (5) To study the effects of extracellular Mg2+ on the intracellular ions in heart cells and on cardiac bioenergetics; (6) To investigate the role of intracellular Na+ and free calcium in the mechanism of lead-induced hypertension and to test the hypothesis that a primary lesion in lead toxicity at the cellular level is a perturbation of cellular sodium homeostasis; (7) To characterize the state of Na+ and K+ ions in normal and sickle red blood cells in oxygenated and deoxygenated states: and (8) To determine the NMR-visibility of Na+ in the interstitial spaces and to develop the technique of double quantum-filtered 23 Na NMR for the selective detection of intracellular Na+ in intact perfused organs using a paramagnetic reagent to quench the extracellular signal.