Differential response of bipolar and normal control lymphoblastoid cell sodium pump to ethacrynic acid

Background: While the pathogenesis of manic-depressive, or bipolar, illness is unknown, an excess of intracellular sodium and calcium concentrations is thought to contribute to the development of the illness. Previous work has demonstrated a reduced adaptive response of the sodium pump to ethacrynic acid in lymphocytes obtained from bipolar subjects compared to psychiatrically normal controls. Methods: To further examine this phenomenon, we investigated several aspects of sodium pump response (transcription, translation, activity, and intracellular ion concentration) in lymphoblastoid cell lines derived from bipolar subjects and matched normal controls. Cells were treated with ethacrynic acid 100 μM for 3 days. Results: Normal control-derived cells exhibited an upregulation of sodium pump mRNA synthesis, protein expression, pump-specific binding and activity, and were able to maintain a normal intracellular sodium concentration. Cells derived from bipolar individuals did not alter sodium pump parameters in any way, and consequently, had a higher intracellular sodium concentration. Limitations: While bipolar lymphoblasts were from an inbred Old Order Amish population, the normal controls were from an outbred population. Conclusions: The results suggest that bipolar illness is associated with an abnormality in cellular sodium homeostatic regulation.