Arcangeli A, Rosati B, Cherubini A, Crociani O, Fontana L, Passani B, Wanke E, Olivotto M
Institute of General Pathology, University of Florence, Italy.
Biochem Biophys Res Commun. 1998 Mar 27;244(3):706-11. doi: 10.1006/bbrc.1998.8319.
The modulation of inward K+ conductances was studied during neuronal differentiation of human SH-SY5Y neuroblastoma cells. Under standard culture conditions, these cells express the herg gene, and the HERG current is the main inward K+ current regulating their Vrest. After 10-20 days exposure to Retinoic Acid (RA), SH-SY5Y cells showed, in addition to HERG currents, a novel current characterized by inward rectification, dependence on the extracellular K+ concentration, and blockade by Cs+ and Ba2+, the main features of the IRK1 current. The appearance of this current is accompanied by a strong hyperpolarisation of Vrest. RT-PCR experiments confirmed that a transcript of the IRK1 (Kir 2.1) gene actually appears in SH-SY5Y cells treated for 10-20 days with RA. On the whole, data here presented demonstrate that RA-induced neuronal differentiation of neuroblastoma cells is accompanied by the switch from a HERG-driven to a IRK1-driven control of Vrest, similarly to what happens in normal differentiating neurons; however, in tumor cells, this switch does not imply the abolition of HERG channel expression.
在人SH-SY5Y神经母细胞瘤细胞的神经元分化过程中，研究了内向钾离子电导的调节。在标准培养条件下，这些细胞表达herg基因，HERG电流是调节其静息电位的主要内向钾离子电流。在暴露于视黄酸（RA）10 - 20天后，SH-SY5Y细胞除了有HERG电流外，还显示出一种新的电流，其特征为内向整流、依赖细胞外钾离子浓度以及被Cs +和Ba2 +阻断，这些是IRK1电流的主要特征。这种电流的出现伴随着静息电位的强烈超极化。RT-PCR实验证实，在用RA处理10 - 20天的SH-SY5Y细胞中确实出现了IRK1（Kir 2.1）基因的转录本。总体而言，此处呈现的数据表明，神经母细胞瘤细胞的RA诱导神经元分化伴随着从HERG驱动到IRK1驱动的静息电位控制的转变，这与正常分化神经元中的情况类似；然而，在肿瘤细胞中，这种转变并不意味着HERG通道表达的消除。
