Effects of lithium isotopes on sodium/lithium co-transport and calcium efflux through the sodium/calcium/lithium exchanger in mitochondria
Bibliographic record
Abstract
The effects of lithium (Li) isotopes and their impact on biological processes have recently gained increased attention due to the significance of Li as a pharmacological agent and the potential that Li isotopic effects in neuroscience contexts may constitute a new example of quantum effects in biology. Previous studies have shown that the two Li isotopes, which differ in mass and nuclear spin, have unusual different effects in vivo and in vitro and, although some molecular targets for Li isotope fractionation have been proposed, it is not known whether those result in observable downstream neurophysiological effects. In this work we studied fluxes of Li + , sodium (Na + ) and calcium (Ca 2+ ) ions in the mitochondrial sodium/calcium/lithium exchanger (NCLX), the only transporter known with recognized specificity for Li + . We studied the effect of Li + isotopes on Ca 2+ efflux from heart mitochondria in comparison to natural Li + and Na + using Ca 2+ -induced fluorescence and investigated a possible Li isotope fractionation in mitochondria using inductively coupled plasma mass spectrometry (ICP-MS). Our fluorescence data indicate that Ca 2+ efflux increases with higher concentrations of either Li + or Na + . We found that the simultaneous presence of Li + and Na + increases Ca 2+ efflux compared to Ca 2+ efflux caused by the same concentration of Li + alone. However, no differentiation in the Ca 2+ efflux between the two Li + isotopes was observed, either for Li + alone or in mixtures of Li + and Na + . Our ICP-MS data demonstrate that there is selectivity between Na + and Li + (greater Na + than Li + uptake) and, most interestingly, between the Li + isotopes (greater 6 Li + than 7 Li + uptake) by the inner mitochondrial membrane. In summary, we observed no Li + isotope differentiation for Ca 2+ efflux in mitochondria via NCLX but found a Li + isotope fractionation during Li + uptake by mitochondria with NCLX active or blocked. Our results suggest that the transport of Li + via NCLX is not the main pathway for Li + isotope fractionation and that this differentiation does not affect Ca 2+ efflux in mitochondria. Therefore, explaining the puzzling effects of Li + isotopes observed in other contexts will require further investigation to identify the molecular targets for Li + isotope differentiation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".