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首页> 外文期刊>The European Journal of Neuroscience >Voltage-gated K current: a marker for apoptosis in differentiating neuronal progenitor cells?
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Voltage-gated K current: a marker for apoptosis in differentiating neuronal progenitor cells?

机译：电压门控K电流：分化神经元祖细胞凋亡的标志？

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Abstract We investigated apoptosis during early stages of in vitro differentiation of neuronal precursors generated by embryonic day 14 (E14) mouse striata stem cells. Differentiation was in conditions of suboptimal growth factor supply. Apoptosis reached 10-15% of cells and affected proliferating as well as postmitotic cells, including TUJ1-positive cells. Inhibition of apoptosis led to an increased proportion of TUJ1-positive cells generated by stem cells. K(+) current was reported to be related to apoptosis. Outward K(+) currents were present in differentiating neuronal precursors that were consistent with delayed rectifier and transient A-type currents. The amplitude of the delayed rectifier current varied during the first 4 days of stem cell differentiation. Current amplitude was greatly increased in the presence of staurosporine but reduced at elevated extracellular K(+) concentration. In addition, the amplitude of the current was significantly diminished by inhibiting several caspases, but not caspase 8. In Bax knock-out transgenic neuronal precurors, K(+) current was not decreased after the first day but at later stages of cell differentiation. At this early stage, apoptosis of proliferating cells and of TUJ1-positive cells was not reduced by the absence of Bax, but was by caspase 9 inhibition. Thus, activation of a delayed rectifier K(+) current in differentiating stem cells is related to apoptosis. Recordings of this current revealed that apoptosis at early stages of neuronal differentiation occurred in two phases that did not exhibit similar dependence on the proapoptotic protein Bax and that probably used different pathways.
机译：摘要我们研究了胚胎第14天（E14）小鼠纹状体干细胞体外分化神经元前体的早期凋亡。分化是在生长因子供应不足的条件下进行的。凋亡达到细胞的10-15％，并影响增殖以及有丝分裂后细胞，包括TUJ1阳性细胞。凋亡的抑制导致干细胞产生的TUJ1阳性细胞比例增加。 K（+）电流被报告与凋亡有关。分化的神经元前体中存在向外的K（+）电流，这与延迟整流器和瞬态A型电流一致。在干细胞分化的前4天中，延迟整流器电流的幅度变化。在存在星形孢菌素的情况下，电流幅度大大增加，但在细胞外K（+）浓度升高时，电流幅度减小。另外，通过抑制几种胱天蛋白酶而不是半胱天冬酶8，电流的幅度被显着减小。在Bax敲除的转基因神经元前体中，K（+）电流在细胞分化的第一天之后并没有降低。在此早期阶段，不存在Bax并不会减少增殖细胞和TUJ1阳性细胞的凋亡，但会受到caspase 9抑制作用的降低。因此，分化干细胞中延迟整流器K（+）电流的激活与细胞凋亡有关。该电流的记录表明，在神经元分化的早期阶段的凋亡发生在两个阶段，这两个阶段对凋亡蛋白Bax的依赖性不同，并且可能使用了不同的途径。

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