Measurement of cation transport in vivo in healthy volunteers after the oral administration of lithium carbonate

Abstract

1. We have measured cation transport in vivo in seven healthy volunteers under control conditions and after they had taken lithium carbonate for 21 days in doses which maintained the serum lithium concentration in the range 0.6-0.8 mmol/l. 2. We have measured cation transport in vivo after the administration of an oral load of rubidium chloride, and have found that, although intra-erythrocytic concentrations of rubidium were significantly lower 1 h after the administration of rubidium when the subjects were taking lithium, there was a significant increase in the rate of uptake of rubidium into the erythrocytes over the subsequent period of the test, suggesting a direct stimulation of sodium, potassium-activated adenosine triphosphatase by lithium. 3. Lithium administration did not affect the plasma concentration versus time profile of rubidium after the rubidium load, implying that the lithium-stimulated uptake of rubidium which occurs in erythrocytes does not necessarily occur in other cell types. 4. These results suggest that previous studies of cation transport using peripheral cells and assay systems in vitro do not necessarily reflect changes in cation transport in vivo in excitable tissues.

Increase in Na+/K+ pump numbers in vivo in healthy volunteers taking oral lithium carbonate and further upregulation in response to lithium in vitro.

“…It is also consistent with our previous finding that the activity of the Na+/K+ pump in vivo increased in the erythrocytes of healthy volunteers after 21 days of in vivo lithium administration (Wood et al, 1989b).…”

“…Neither the results of our present ouabain binding experiment nor our previous in vivo Na+/K+ pump activity experiment (Wood et al, 1989b) is consistent with the earlier results of Naylor et al (1977). Those investigators demonstrated a small fall in Na+/K+ pumpmediated potassium uptake into erythrocytes ex vivo after lithium treatment, but no change in Na+,K+-ATPase activity, measured as the rate of hydrolysis of ATP.…”

“…By contrast, the rate constant for Na+/K+ flux activity in erythrocytes in the in vivo study of Wood et al (1989b) was doubled after 21 days of lithium in vivo. Although this difference might simply represent a difference between erythrocytes and lymphocytes, it suggests that only part of the increase in Na+/K+ pump activity in response to lithium in vivo is attributable to an increase in pump number and that there is probably also an increase in the activity of individual pump sites.…”

Time course of acute neuroprotective effects of lithium carbonate evaluated by brain impedanciometry in the global ischemia model

“…Neuronal survival and degeneration after ischemia depends on the intracellular ATP supply and ion homeostasis (Martínez-Sánchez et al 2004). The strong edema-reducing effect of lithium reported here, more intense for the first 10 min of ischemia, can be a product of the stimulating action of lithium on Na/K-ATPase and MgATPase activities, which was reported in blood red cells (Glen et al 1972;Glen and Reading 1973;Dick et al 1974;Hesketh et al 1978;Wood et al 1989a), brain synaptosome Na/K-ATPase (Wood et al 1989b), or by increase in the number of Na/K-ATPases (Young 2009), but not by an increase in energy metabolites, as was shown by Lin et al (1993); thus, lithium can normalize abnormally elevated intracellular sodium levels induced by ouabain in human glioma cells (Huang et al 2007). Additionally, lithium selectively inhibits Na + influx through Na + channels and subsequent Ca 2+ influx and catecholamine secretion, independent of glycogen synthase kinase 3 inhibition (Yanagita et al 2007).…”