Arsenic trioxide-induced hela cell death is partially prevented by K+ channel blockers / 药学学报

ABSTRACT

<p><b>AIM</b>To investigate the effects of K+ channel blockers on arsenic trioxide-induced HeLa cell death.</p><p><b>METHODS</b>Viability of HeLa cells was assessed by mitochondrial dehydrogenase activity using colorimetric MTT assay and the voltage-dependent K+ currents were recorded by using patch-clamp technique.</p><p><b>RESULTS</b>Exposure of As2O3 (5 micromol x L(-1)) for 24 h caused marked HeLa cell death. The rest living cells after As2O3 24 h-incubation showed significant increase of K+ currents densities. At +80 mV, the densities of K+ currents (61 +/- 18) pA/10 pF (n = 8) in As2O3 24 h-incubation group were significantly more than that in the control group (38 +/- 10) pA/10 pF (n = 8, P < 0.05). The HeLa cells were prevented partially from As2O3-induced cell death by co-application for 24 h with typical voltage-dependent K+ channel blockers, 4-aminopyridine (3 mmol x L(-1)) or tetraethylammonium (5 mmol x L(-1)). 4-Aminopyridine (3 mmol x L(-1)) or tetraethylammonium (5 mmol x L(-1)) did not show any toxic effects on HeLa cells.</p><p><b>CONCLUSION</b>Chronic treatment with As2O3 increased voltage-dependent K+ currents in HeLa cells and the cell death induced by As2O3 was reduced partially by voltage-dependent K+ channel blockers, 4-aminopyridine or tetraethylammonium.</p>