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

Abstract

1. We have measured [3H]‐ouabain binding to lymphocyte membranes in eight healthy volunteers before and after they had taken lithium carbonate for 14 days in doses which maintained the serum lithium concentration in the range 0.5‐1.0 mmol 1‐1. 2. There was a statistically significant increase in the [3H]‐ouabain binding capacity of the lymphocyte membranes (reflecting the number of Na+, K+‐ATPase molecules) after 14 days of lithium administration in vivo. This suggests that a failure to increase pump numbers after similar exposure to lithium in vivo in patients with manic‐depressive psychosis is a primary abnormality associated with the disease. 3. In vivo lithium administration did not alter the normal adaptive (upregulatory) response of lymphocyte Na+, K+‐ATPase to standard pharmacological challenges, involving in vitro incubation for 3 days with lithium chloride (8 mmol 1‐1) or sodium ethacrynate (1 mumol 1‐1). 4. We have previously found that there is an impaired response of the Na+, K+‐ ATPase to these in vitro stimuli in patients with manic‐depressive psychosis, and our present data suggest that this abnormality is attributable to the disease itself and not to in vivo lithium therapy. 5. The data also suggest that the increase in vivo Na+/K+ pump activity which we have previously described in healthy volunteers after 21 days of lithium administration is at least partly due to an increase in Na+/K+ pump numbers.

Meta-analysis of erythrocyte Na,K-ATPase activity in bipolar illness

“…The decrease in activity among bipolars is seen only when ill individuals are compared with euthymic patients, and occurs independently of the type of treatment [Li alone (Naylor et al, 1973Nurnberger et al, 1982), antidepressant alone (Nurnberger et al, 1982;Rybakowski et al, 1981), various combinations of drugs (Nurnberger et al, 1982), or ECT alone (Choi et al, 1977)], as well as in unmedicated patients (Naylor et al, 1973Rybakowski et al, 1981). The apparent lack of medication effect is consistent with the observation that lymphocytes obtained from bipolar individuals do not upregulate Na,K-ATPase when exposed to lithium as do cells obtained from normal controls or unaffected family members of bipolar probands (Antia et al, 1992(Antia et al, , 1995Wood et al, 1991). The finding that Na,K-ATPase activity in bipolar patients is not different from that in control is consistent with the interpretation that this is a state-dependent, rather than a trait-related, phenomenon.…”

SEX DIFFERENCES IN HUMAN LYMPHOCYTE Na,K-ATPase AS STUDIED BY LABELED OUABAIN BINDING

“…Sex-related differences in lymphocyte Na,K-ATPase may solely be related to their activability (Vereninov et al, 1993;Buttgereit et al, 2000;Marakhova et al, 2005). However, if the idea that lymphocyte Na,K-ATPase may represent its brain counterpart is correct (Antia et al, 1992(Antia et al, , 1995 these results might have broader implications.…”

“…of its activity in connection with brain physio-pathological states (Antia et al, 1992(Antia et al, , 1995.…”