Lithium-potassium interaction in acutely treated cortical neurons and astrocytes

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+.