BACKGROUND The hERG potassium channel can modulate the proliferation of the chronic myelogenous leukemic K562 cells, and its role in the erythroid differentiation of K562 cells still remains unclear. PRINCIPAL FINDINGS The hERG potassium channel blockage by a new 36-residue scorpion toxin BmKKx2, a potent hERG channel blocker with IC50 of 6.7 ± 1.7 nM, enhanced the erythroid differentiation of K562 cells. The mean values of GPA (CD235a) fluorescence intensity in the group of K562 cells pretreated by the toxin for 24 h and followed by cytosine arabinoside (Ara-C) treatment for 72 h were about 2-fold stronger than those of K562 cells induced by Ara-C alone. Such unique role of hERG potassium channel was also supported by the evidence that the effect of the toxin BmKKx2 on cell differentiation was nullified in hERG-deficient cell lines. During the K562 cell differentiation, BmKKx2 could also suppress the expression of hERG channels at both mRNA and protein levels. Besides the function of differentiation enhancement, BmKKx2 was also found to promote the differentiation-dependent apoptosis during the differentiation process of K562 cells. In addition, the blockage of hERG potassium channel by toxin BmKKx2 was able to decrease the intracellular Ca(2+) concentration during the K562 cell differentiation, providing an insight into the mechanism of hERG potassium channel regulating this cellular process. CONCLUSIONS/SIGNIFICANCE Our results revealed scorpion toxin BmKKx2 could enhance the erythroid differentiation of leukemic K562 cells via inhibiting hERG potassium channel currents. These findings would not only accelerate the functional research of hERG channel in different leukemic cells, but also present the prospects of natural scorpion toxins as anti-leukemic drugs.

中文翻译：

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蝎毒 BmKKx2 对 hERG 钾通道的阻断增强了人白血病细胞 K562 的红细胞分化。

背景hERG钾通道可调节慢性粒细胞白血病K562细胞的增殖，其在K562细胞红细胞分化中的作用尚不清楚。主要发现 一种新的 36 残基蝎毒素 BmKKx2（一种有效的 hERG 通道阻滞剂，IC50 为 6.7 ± 1.7 nM）对 hERG 钾通道的阻断增强了 K562 细胞的红细胞分化。毒素预处理 24 h 后用阿糖胞苷 (Ara-C) 处理 72 h 的 K562 细胞组 GPA (CD235a) 荧光强度的平均值是 K562 细胞的 2 倍。单独的 Ara-C。hERG 钾通道的这种独特作用也得到了证据的支持，即毒素 BmKKx2 对细胞分化的影响在 hERG 缺陷细胞系中无效。在 K562 细胞分化过程中，BmKKx2 还可以在 mRNA 和蛋白质水平上抑制 hERG 通道的表达。除了促进分化的功能外，还发现BmKKx2在K562细胞分化过程中促进分化依赖性细胞凋亡。此外，毒素 BmKKx2 对 hERG 钾通道的阻断能够降低 K562 细胞分化过程中的细胞内 Ca(2+) 浓度，从而深入了解 hERG 钾通道调节这一细胞过程的机制。结论/意义 我们的结果表明蝎毒 BmKKx2 可以通过抑制 hERG 钾通道电流来增强白血病 K562 细胞的红细胞分化。