Na-23 multiple quantum filtered NMR characterisation of Na+ binding and dynamics in animal cells: a comparative study and effect of Na+/Li+ competition

Double quantum and triple quantum filtered Na-23 nuclear magnetic resonance techniques were used to characterise in detail the isotropic and anisotropic binding and dynamics of intra- and extracellular Na+ in different cellular systems, in the absence and presence of Li+. The kinetics of Li+ influx by different cell types was evaluated. At steady state, astrocytes accumulated more Li+ than red blood cells (RBCs), while a higher intracellular Li+ concentration was found in chromaffin than in SH-SY5Y cells. Anisotropic and isotropic motions were detected for extracellular Na+ in all cellular systems studied. Isotropic intracellular Na+ motions were observed in all types of cells, while anisotropic Na+ motions in the intracellular compartment were only detected in RBCs. Na-23 triple quantum signal efficiency for intracellular Na+ was SH-SY5Y > chromaffin > RBCs, while the reverse order was observed for the extracellular ions. Na-23 double quantum signal efficiency for intracellular Na+ was non-zero only in RBCs, and for extracellular Na+ the order RBCs > chromaffin > SH-SY5Y cells was observed. Li+ loading generally decreased intracellular Na+ isotropic movements in the cells, except for astrocytes incubated with a low Li+ concentration and increased anisotropic intracellular Na+ movements in RBCs. Li+ effects on the extracellular signals were more complex, reflecting Li+/Na+ competition for isotropic and anisotropic binding sites at the extracellular surface of cell membranes and also at the surface of the gel used for cell immobilisation. These results are relevant and contribute to the interpretation of the in vivo pharmacokinetics and sites of Li+ action.