Arsenic trioxide-induced hela cell death is partially prevented by K+ channel blockers.
OBJECTIVE
To investigate the effects of K+ channel blockers on arsenic trioxide-induced HeLa cell death.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dong
De-Li
DL
Department of Pharmacology, Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150086, China. dldong@tom.com
Song
Wei-Hua
WH
Pei-Lin
Yang
Bao-Feng
BF
D015761:4-Aminopyridine / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D010087:Oxides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects; D019789:Tetraethylammonium / Q000494:pharmacology*
D001152:Arsenicals; D010087:Oxides; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D000077237:Arsenic Trioxide