Walz W, Hertz E, Hertz L
Prog Neuropsychopharmacol Biol Psychiatry. 1983;7(4-6):697-702. doi: 10.1016/0278-5846(83)90048-9.
Pure mouse primary cultures of cortical astrocytes and of cortical neurons were exposed to 1 mM Li+, i.e., a therapeutically relevant concentration. The 42K uptake rates of neurons were not influenced, whereas those of astrocytes showed an 11% inhibition (P less than 0.01). Internal loading with Li+ did not change the K+ uptake rates in either cell type. Neurons, which had been exposed for 5 min to veratridine, a situation which mimics neuronal activity, showed also no change in K+ uptake rate when Li+ was present during this time. Na+-K+ ATPase activity from cell homogenates was not changed in neuronal preparations by exposure to Li+, but astrocytic preparations appeared to show a slight increase by 14%. These experiments point out that the Li+ effects on ion distribution of the brain which have been described in the literature, are due to partly impairment of astrocytic K+ uptake. The mechanism of action, underlying the Li+ effect is probably a competition with K+ for transport sites at the external site of the Na+-K+ ATPase. This leads to a decrease of K+ uptake, but an enhancement of ATPase activity in the presence of Li+.
将纯的小鼠皮质星形胶质细胞和皮质神经元原代培养物暴露于1 mM Li⁺,即治疗相关浓度。神经元的42K摄取率未受影响,而星形胶质细胞的摄取率则受到11%的抑制(P小于0.01)。Li⁺的内部加载对两种细胞类型的K⁺摄取率均无影响。暴露于藜芦碱5分钟的神经元,模拟神经元活动的情况,在此期间存在Li⁺时,K⁺摄取率也没有变化。通过暴露于Li⁺,神经元匀浆中的Na⁺-K⁺ ATP酶活性没有改变,但星形胶质细胞匀浆似乎略有增加,增加了14%。这些实验指出,文献中描述的Li⁺对脑离子分布的影响,部分是由于星形胶质细胞K⁺摄取受损。Li⁺作用的潜在机制可能是与K⁺竞争Na⁺-K⁺ ATP酶外部位点的转运位点。这导致K⁺摄取减少,但在存在Li⁺的情况下ATP酶活性增强。