This report expands on previously presented evidence for a trait-dependent deficiency of erythrocyte sodium pump activity in bipolar affective disorder. Several parameters of erythrocyte NaK-ATPase activity in different affective states and the effects of lithium therapy were examined. In lithium-free bipolar affective disorder patients, the mean percent differences from the individual sex- and age-matched controls for erythrocyte sodium pump activity were: manic + hypomanic group, -21.5%, n = 16, p less than 0.02; depressed group, -12.4%, n = 14, p less than 0.02; euthymic group, -6.9%, n = 18, p less than 0.10. Ouabain-sensitive potassium ion uptake was less than the controls in the manic group (-25.4%, n = 3, p less than 0.02), and in the combined affectively ill group, manic + depressed (-23.4%, n = 7, p less than 0.02). Cell ouabain binding was less than the controls in the manic group (-19.0%, n = 6, p less than 0.05). NaK-ATPase activity in washed erythrocyte membranes (ghosts) was significantly lower than the controls in the manic group (-14.5%, n = 4, p less than 0.02), and the mean value for the whole group (manic + depressed + euthymic) was lower than the controls (-11.8%, n = 18, p less than 0.05). Values for ouabain binding in ghosts from the bipolar subjects were not significantly different from the matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC, USA. Electronic address:
Our laboratory has recently demonstrated that low concentrations of ouabain increase blood pressure in rats associated with stimulation of NaK ATPase activity and activation of the Src signaling cascade in NHE1-dependent manner. Proteomic analysis of human kidney proximal tubule cells (HKC11) suggested that the Angiotensin II type 1 receptor (AT1R) as an ouabain-associating protein. We hypothesize that ouabain-induced stimulation of NaK ATPase activity is mediated through AT1R.
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