Altered intracellular calcium level in association with neuronal death induced by lithium chloride

In this study, we examined the effects of lithium chloride (LiCl) on the intracellular calcium levels ([Ca²⁺](i)), and the survival of immature and mature cultured cerebellar granule neurons (CGNs) grown in medium containing high (25 mmol/L) or normal (5 mmol/L) potassium (K⁺) levels. LiCl dramatically reduced [Ca²⁺](i) in immature CGNs maintained in high K⁺ (HK) medium and in those switched to serum containing normal K⁺ (NK) medium for 1 to 2 days. This reduction in [Ca²⁺](i) led to massive neuronal death of immature neurons developed in both HK and NK medium. In mature (cultured 5-8 days in vitro) CGNs, LiCl exhibited potent toxicity when cells were grown in HK medium, and led to increased [Ca²⁺](i). Exposing mature CGNs to serum deprivation and normal extracellular K⁺ concentrations decreased [Ca²⁺](i) and induced cell death, while the addition of LiCl in these conditions further decreased [Ca²⁺](i) but prevented cell death. The morphologic features revealed by Nomarski optics further confirmed these effects of LiCl on neuronal survival. Together, these findings indicate that the effects of LiCl on [Ca²⁺](i) and neuronal death, and the association between [Ca²⁺](i) and cell death, depend on the developmental stage of CGNs and the growth conditions to which they are subjected. These findings may help in understanding the mechanism of neurotoxicity of LiCl during therapy.