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Cardiac specific transcription factor Csx/Nkx2.5 regulates transient-outward K + channel expression in pluripotent P19 cell-derived cardiomyocytes
The Journal of Physiological Sciences ( IF 2.6 ) Pub Date : 2020-03-25 , DOI: 10.1186/s12576-020-00748-z
Tomoko Uchino , Ming-Qi Zheng , Yan Wang , Katsushige Ono

The homeobox-containing gene Csx/Nkx2.5 codes several cardiac transcription factors and plays a critical role in early cardiogenesis. We investigated the effect of Csx/Nkx2.5 on the expression of cardiac ion channels using P19-derived cardiomyocytes. P19CL6 cells and P19CL6 cells with Csx/Nkx2.5 overexpression (P19CL6-Csx cells) were induced to differentiate into cardiomyocytes by treatment with dimethyl sulfoxide. Action potentials and membrane currents were measured by whole cell patch clamp at different differentiation stage: the early stage (1–5 days after beating had begun) and the late stage (10–15 days after beating). Expression of Csx/Nkx2.5 mRNA was increased as the differentiation stages advanced in both P19CL6 and P19CL6-Csx cells. In action potential configuration, maximal diastolic potentials in P19CL6-Csx cells exhibited more hyperpolarized potential (‒ 64.2 mV) than those in P19CL6 cells (‒ 54.8 mV, p  < 0.01) in the early stage. In P19CL6 cells, among 6 different voltage-gated and ligand-operated K+ channels expressed during the early stage, the transient-outward K+ channel was most predominant. By overexpression of Csx/Nkx2.5, developmental decrease in the transient-outward K+ channel was suppressed. Homeobox-containing gene Csx/Nkx2.5 modifies the amount of distinct ionic channels, during differentiation periods, predominantly changing the expression of the transient-outward K+ channel.

中文翻译:

心脏特异性转录因子Csx / Nkx2.5调节多能性P19细胞来源的心肌细胞中的瞬时向外K +通道表达

包含同源盒的基因Csx / Nkx2.5编码几种心脏转录因子,并在早期心脏发生中起关键作用。我们调查了Csx / Nkx2.5对使用P19衍生的心肌细胞表达心脏离子通道的影响。通过用二甲基亚砜处理,诱导Csx / Nkx2.5过表达的P19CL6细胞和P19CL6细胞(P19CL6-Csx细胞)分化为心肌细胞。通过全细胞膜片钳在不同的分化阶段测量动作电位和膜电流:早期(开始搏动后1–5天)和晚期(搏动后10–15天)。随着P19CL6和P19CL6-Csx细胞分化阶段的进展,Csx / Nkx2.5 mRNA的表达增加。在实际操作中, p  <0.01)。在P19CL6细胞中,在早期表达的6个不同的电压门控和配体操作的K +通道中,瞬时向外K +通道最为主要。通过Csx / Nkx2.5的过表达,抑制了瞬时向外K +通道的发育下降。包含同源盒的基因Csx / Nkx2.5在分化期修改了不同离子通道的数量,主要改变了瞬时向外K +通道的表达。
更新日期:2020-03-25
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