Quantitation of intracellular [Na⁺] in vivo by using TmDOTP^5- as an NMR shift reagent and extracellular marker

A method is presented to measure the absolute concentration of intracellular Na⁺ ([Na⁺](i)) in vivo by using interleaved ²³Na- and ³¹P-nuclear magnetic resonance (NMR) spectroscopy and TmDOTP^5- as shift reagent and chemical marker of tissue extracellular space (ECS). The technique was used to determine [Na⁺](i) and relative ECS in livers of control rats (21 ± 3 and 0.11 ± 0.02 mM, respectively) and in rats exposed to carbon tetrachloride (103 ± 29 and 0.23 ± 0.03 mM, respectively). The NMR measurements were confirmed independently on excised tissue samples by using atomic absorption spectroscopy. The results confirm that TmDOTP^5- can be used as a combined cation shift reagent and ECS marker, thereby allowing quantitation of [Na⁺](i) in vivo by NMR.