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Background: Ethacrynic acid (ECA), a diuretic that has several cellular actions, increases expression of the sodium and potassium-activated adenosine triphosphatase (Na, K-ATPase or Na pump) in normal lymphocytes, but not in lymphocytes of bipolar patients. While this has been proposed to be important in the pathophysiology of bipolar illness, the response of neural tissues to ECA is unknown., Methods: Human neuroblastoma SH-SY5Y cells differentiated with 10-microM retinoic acid were treated with various ECA concentrations for 3 days, and changes in Na-pump alpha-isoform expression were quantified with densitometric analysis of Western bands., Results: Expression of alpha1 and alpha3 Na pump isoforms significantly increased with 10-5 M ECA. Cells treated with 10-6 or 10-7 M ECA showed no change in Na-pump expression, while cells treated with 10-4 M ECA died. The alpha2 isoform could not be detected in differentiated SH-SY5Y cells., Conclusions: The effect of ECA on alpha1-isoform in neural tissue is similar to that observed in lymphocytes. As alpha3 isoform is not expressed in lymphocytes, however, we conclude that lymphocytes are an incomplete model of neural tissue.