Kerr Niall C H, Gao Zhan, Holmes Fiona E, Hobson Sally-Ann, Hancox Jules C, Wynick David, James Andrew F
Department of Pharmacology, South Bristol, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK.
Mol Cell Neurosci. 2007 Jun;35(2):283-91. doi: 10.1016/j.mcn.2007.03.002. Epub 2007 Mar 13.
Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with little or no expression reported postnatally. We report here the expression of Nav1.5 mRNA isoforms in adult mouse and rat DRG. The major isoform of mouse DRG is Nav1.5a, which encodes a protein with an IDII/III cytoplasmic loop reduced by 53 amino acids. Western blot analysis of adult mouse DRG membrane proteins confirmed the expression of Nav1.5 protein. The Na+ current produced by the Nav1.5a isoform has a voltage-dependent inactivation significantly shifted to more negative potentials (by approximately 5 mV) compared to the full-length Nav1.5 when expressed in the DRG neuroblastoma cell line ND7/23. These results imply that the alternatively spliced exon 18 of Nav1.5 plays a role in channel inactivation and that Nav1.5a is likely to make a significant contribution to adult DRG neuronal function.
Nav1.5是心脏中主要表达的电压门控钠通道,在胚胎背根神经节(DRG)中也有较低丰度的表达,而出生后几乎没有或没有表达的报道。我们在此报告Nav1.5 mRNA亚型在成年小鼠和大鼠DRG中的表达。小鼠DRG的主要亚型是Nav1.5a,它编码一种蛋白,其IDII/III胞质环减少了53个氨基酸。对成年小鼠DRG膜蛋白的蛋白质印迹分析证实了Nav1.5蛋白的表达。当在DRG神经母细胞瘤细胞系ND7/23中表达时,与全长Nav1.5相比,Nav1.5a亚型产生的Na+电流具有明显向更负电位(约5 mV)偏移的电压依赖性失活。这些结果表明,Nav1.5的选择性剪接外显子18在通道失活中起作用,并且Nav1.5a可能对成年DRG神经元功能有重大贡献。