钾通道阻断剂部分抑制三氧化二砷诱导的HeLa细胞死亡

目的研究钾通道阻滞剂对三氧化二砷诱导的HeLa细胞死亡的作用。方法采用MTT法评价HeLa细胞的存活情况，采用膜片钳技术记录HeLa细胞的电压依赖性钾电流。结果As₂O₃(5 μmol·L^-1)孵育24 h引起显著的HeLa细胞死亡，As₂O₃(5 μmol·L^-1)孵育24 h后存活的细胞表现明显的电压依赖性钾电流密度增加。+80 mV电压下，As₂O₃(5 μmol·L^-1)孵育组电流密度(61±18) pA/10 pF(n=8)明显高于对照组(38±10) pA/10 pF(n=8,P<005)。As₂O₃诱导的HeLa细胞死亡可被共同孵育钾通道阻滞剂四氨基吡啶(3 mmol·L^-1)或四乙基铵(5 mmol·L^-1)所部分抑制。3 mmol·L^-1四氨基吡啶或5 mmol·L^-1四乙基铵对HeLa细胞无明显细胞毒作用。结论As₂O₃长期处理增加HeLa细胞的电压依赖性钾电流。As₂O₃诱导的HeLa细胞死亡可被钾通道阻滞剂四氨基吡啶或四乙基铵部分抑制。

Arsenic trioxide-induced HeLa cell death is partially prevented by K+ channel blockers

AIM: 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. CONCLUSION: 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.