Effect of ethacrynic acid on sodium pump α isoforms in SH-SY5Y cells

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‐μM retinoic acid were treated with various ECA concentrations for 3 days, and changes in Na‐pump α‐isoform expression were quantified with densitometric analysis of Western bands. Results: Expression of α1 and α3 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 α2 isoform could not be detected in differentiated SH‐SY5Y cells. Conclusions: The effect of ECA on α1‐isoform in neural tissue is similar to that observed in lymphocytes. As α3 isoform is not expressed in lymphocytes, however, we conclude that lymphocytes are an incomplete model of neural tissue.