Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents.

Indapamide blocks multiple voltage-dependent K+ currents (Kv) in the heart and Kv have an important role in cell proliferation and apoptosis, so the aim of this work was to study the effects of indapamide on Kv and the viability of GH3 cells. Indapamide inhibited Kv of GH3 cells and the inhibition was irreversible after a 10-min washout when more than 250 microM indapamide was used. Indapamide reduced the viability of GH3 cells in a concentration-dependent manner. The decreased cell viability was because indapamide induced cell apoptosis, or even necrosis at higher concentrations. HepG2 cells, which express no apparent Kv, were used to determine the association between inhibition of Kv and the apoptotic action of indapamide. Indapamide had a similar action on cell viability and apoptosis of HepG2 cells. 4-Aminopyridine, the voltage-dependent K+ channel blocker, inhibited Kv of GH3 cells but did not induce the cell apoptosis. We concluded that while indapamide inhibited Kv and induced apoptosis of GH3 cells, the apoptotic action of indapamide was not associated with its inhibition of Kv.