Chen Yau-Hung, Huang Fong-Lee, Cheng Yi-Chuan, Wu Chia-Jung, Yang Cheng-Ning, Tsay Huey-Jen
Graduate Institute of Life Sciences, Tamkang University, Taipei, Taiwan.
J Biomed Sci. 2008 Jan;15(1):69-78. doi: 10.1007/s11373-007-9200-4. Epub 2007 Aug 9.
Although multiple subtypes of sodium channels are expressed in most neurons, the specific contributions of the individual sodium channels remain to be studied. The role of zebrafish Na(v)1.6 sodium channels in the embryonic locomotor movements has been investigated by the antisense morpholino (MO) knockdown. MO1 and MO2 are targeted at the regions surrounding the translation start site of zebrafish Na(v)1.6 mRNA. MO3 is targeted at the RNA splicing donor site of exon 2. The correctly spliced Na(v)1.6 mRNA of MO3 morphants is 6% relative to that of the wild-type embryos. Na(v)1.6-targeted MO1, MO2 and MO3 attenuate the spontaneous contraction, tactile sensitivity, and swimming in comparison with a scrambled morpholino and mutated MO3 morpholino. No significant defect is observed in the development of slow muscles, the axonal projection of primary motoneurons, and neuromuscular junctions. The movement impairments caused by MO1, MO2, and MO3 suggest that the function of Na(v)1.6 sodium channels is essential on the normal early embryonic locomotor activities.
尽管大多数神经元中表达多种亚型的钠通道，但各个钠通道的具体作用仍有待研究。通过反义吗啉代寡核苷酸（MO）敲低技术，研究了斑马鱼Na(v)1.6钠通道在胚胎运动中的作用。MO1和MO2靶向斑马鱼Na(v)1.6 mRNA翻译起始位点周围的区域。MO3靶向第2外显子的RNA剪接供体位点。MO3 morphants正确剪接的Na(v)1.6 mRNA相对于野生型胚胎的为6%。与乱序吗啉代寡核苷酸和突变的MO3 morpholino相比，靶向Na(v)1.6的MO1、MO2和MO3减弱了自发收缩、触觉敏感性和游泳能力。在慢肌发育、初级运动神经元的轴突投射和神经肌肉接头方面未观察到明显缺陷。MO1、MO2和MO3引起的运动障碍表明，Na(v)1.6钠通道的功能对于正常的早期胚胎运动活动至关重要。
