7Li Nuclear Magnetic Resonance Study for the Determination of Li+ Properties in Neuroblastoma SH‐SY5Y Cells

: Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH‐SY5Y cells by developing a novel 7Li NMR method that provided a clear estimation of the intra‐ and extracellular amounts of Li+ in the presence of the shift reagent thulium‐1,4,7,10‐tetrazacyclododecane‐N,N′,N″,N‴‐tetramethylene phosphonate (HTmDOTP4−). The first‐order rate constants of Li+ influx and efflux for perfused, agarose‐embedded SH‐SY5Y cells in the presence of 3 mM HTmDOTP4− were 0.055 ± 0.006 (n = 4) and −0.025 ± 0.006 min−1 (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Na+ channel‐mediated Li+ transport in SH‐SY5Y cells. 7Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH‐SY5Y cells than in human RBCs.