title: hERG potassium channel blockage by scorpion toxin BmKKx2 enhances erythroid differentiation of human leukemia cells K562.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Youtian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D000072237:ERG1 Potassium Channel; D041905:Erythroid Cells / Q000378:metabolism* / Q000473:pathology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012604:Scorpion Venoms / Q000494:pharmacology*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C445369:KK toxin, Buthus martensi; D012604:Scorpion Venoms; D002118:Calcium