Effect of lithium isotopes on sodium/lithium/calcium exchanger in mitochondria

Lithium (Li) has been a primary treatment for bipolar disorder for decades, but its mechanism of action remains unclear. Li has two stable isotopes: 6Li and 7Li (natural abundances are 7.5% and 92.5%). These isotopes differ in mass and nuclear spin. Previous studies showed that Li isotopes have different effects on animal behaviour and on electrical response in neuronal tissues. To further investigate these effects, we focused on the sodium/lithium/calcium exchanger (NCLX) in mitochondria, which is a proposed target for Li+ ions. Mitochondria play a crucial role in calcium regulation, affecting synaptic transmission and neuronal signal processing. The study investigates Li isotopes at the single-channel level, potentially revealing quantum effects in ion transport.

Two methods were employed to assess Li isotope transport through NCLX: (i) calcium-induced fluorescence to monitor Ca2+ efflux dynamics and (ii) inductively coupled plasma mass spectrometry (ICP-MS).

Results indicated differences in calcium dynamics with functional NCLX when exposed to Li, Na, or K. However, when examining Li isotopes, no significant distinctions were observed in their partitioning within heart mitochondria or their impact on Ca2+ efflux. These findings suggest that either there is no distinct Li isotope effect on NCLX or that NCLX is not the sole molecular target for Li ions in mitochondria.