Multiple quantum filtered ²³Na NMR in the Langendorff perfused mouse heart: Ratio of triple/double quantum filtered signals correlate with [Na]_i

We investigate the potential of multiple quantum filtered (MQF) ²³Na NMR to probe intracellular [Na]_i in the Langendorff perfused mouse heart. In the presence of Tm(DOTP) shift reagent the triple quantum filtered (TQF) signal originated largely from the intracellular sodium pool with a 32±6 % contribution of the total TQF signal arising from extracellular sodium, whilst the rank 2 double-quantum filtered signal (DQF), acquired with a 54.7° flip-angle pulse, originated exclusively from the extracellular sodium pool. Given the different cellular origins of the ²³Na MQF signals we propose that the TQF/DQF ratio can be used as a semi-quantitative measure of [Na]_i in the mouse heart. We demonstrate a good correlation of this ratio with [Na]_i measured with shift reagent at baseline and under conditions of elevated [Na]_i. We compare the measurements of [Na]_i using both shift reagent and TQF/DQF ratio in a cohort of wild type mouse hearts and in a transgenic PLM^3SA mouse expressing a non-phosphorylatable form of phospholemman, showing a modest but measurable elevation of baseline [Na]_i. MQF filtered ²³Na NMR is a potentially useful tool for studying normal and pathophysiological changes in [Na]_i, particularly in transgenic mouse models with altered Na regulation.