Interestingly, suppression of oocyte condensation and fragmentation could also be reproduced with LiCl, but not with NaCl, indicating some level of ion selectivity for these effects. Although previous in vitro studies with thymocytes indicated that the cell death endpoints studied were equally affected by all monovalent cations, the general similarity in the results across these two studies suggest that ionic strength, as opposed to ionic specificity, is the main modifier. The importance of potassium in vivo is therefore probably due to its high ionic concentration, as opposed to the presence of potassium per se, in the cytoplasm of viable cells. The finding that LiCl was as effective as KCl in preventing some of the biochemical and morphological events associated with apoptosis may be related to the fact that lithium can pass through some types of potassium channels, resulting in an exchange of potassium for lithium inside the cell.
Furthermore, recent studies have shown that LiCl protects rat cerebellar granule cells from apoptosis induced by a number of external stimuli, collectively suggesting that lithium may indeed have pharmacologic similarity to potassium action in this regard. The relative ineffectiveness of NaCl in suppressing apoptotic effects is not surprising because the NaCl medium is essentially normal medium, and the cell expends considerable energy to maintain the Na+ gradient across the membrane. The mechanisms employed are not circumvented in this study, and thus NaCl in the medium would not be expected to affect apoptosis. It should be noted that a small effect of NaCl on DNA degradation was detected in rat follicles, although it was not as strong or complete as seen with K+ or Li+. The ability of Na+ to inhibit apoptotic enzymes in vitro further suggests that ionic strength, as opposed to ionic specificity, is the main modifier of the apoptotic program.