Inhibition of kidney potassium channels by fluoxetine: In vivo and in vitro studies.

In vitro studies have demonstrated that fluoxetine, a commonly used antidepressant drug, can modulate the activity of K + channels. In the present study, we investigated the in vivo effect of acute and sub-chronic treatment of rats with fluoxetine on K + renal transport. Furthermore, OK cells, a kidney epithelial cell line, were used in order to evaluate the in vitro effect of fluoxetine on K + currents. In the sub-chronic study, fluoxetine was administrated daily (10 mg/kg, p.o.) for 15 days to male adult Wistar rats. In the acute study, rats were given increasing doses of fluoxetine (1, 3, 10, 30 and 50 mg/kg, p.o.) for 24 h. Results from the sub-chronic study show that urinary K + content (in mmol/L) was markedly reduced in the fluoxetine-treated animals (fluoxetine: 83 ± 9; control: 131 ± 10; P < 0.001). K + fractional renal excretion (in %) was also significantly lower in the fluoxetine group (fluoxetine: 6 ± 1; control: 13 ± 2; P < 0.001). No significant changes was observed in creatinine clearance and on renal tubular Na + ,K + -ATPase activity. Results obtained from the acute study demonstrate that, after a 24-h administration, fluoxetine produced a dose-dependent decrease in urinary K + , with an ED 50 (in mg/kg) of 4.2 (2.8; 5.5) and a maximal effect of 62% reduction. In vitro, fluoxetine produced a concentration-dependent inhibition of K + currents in OK cells, with an EC 50 of 107 (84.8; 129.5) μM. In conclusion, fluoxetine produces a marked reduction on urinary K + excretion; this effect constitutes an in vivo evidence for the inhibitory action of fluoxetine on kidney epithelial K + channels.