Expression of skeletal muscle Nav1.4 Na channel isoform in canine cardiac Purkinje myocytes
Expression of skeletal muscle Nav1.4 Na channel isoform in canine cardiac Purkinje myocytes
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DOI：
10.1016/j.bbrc.2007.01.101
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发表时间：
2007-03-30
影响因子：
3.1
通讯作者：
Boutjdir, Mohamed
中科院分区：
文献类型：
--
作者：
Qu, Yongxia;Karnabi, Eddy;Boutjdir, Mohamed
背景和目的：浦肯野纤维的动作电位平台对河豚毒素(TTX)特别敏感，这可能是由于TXX敏感的Na+电流所致。已有报道TTX敏感的神经细胞Nav1.1和Nav1.2亚型在犬浦肯野肌细胞中表达。我们的目的是通过生化和功能技术来研究TTX敏感的骨骼Nav1.4亚型是否也在犬心脏浦肯野肌细胞中表达。方法和结果：利用Nav1.4特异性引物，从犬浦肯野纤维RNA中扩增出与Nav1.4相对应的PCR产物，并通过测序和基因库的巨型广播进行验证。与心脏异构体NaV1.5相比，使用抗Nav1.4抗体的共聚焦间接免疫染色显示了不同的肌膜染色模式。在tsA201细胞中表达Nav1.4可产生TTX敏感的钠电流，其IC50为10 nM。结论：犬心脏浦肯野细胞表达TTX敏感的Nav1.4通道。这一新的发现表明Nav1.4通道在浦肯野肌细胞中起作用，因此对起源于浦肯野网络的室性心律失常的机制和治疗具有重要的临床意义。由爱思唯尔公司出版。
Background and Aim: The action potential plateau of Purkinje fibers is particularly sensitive to tetrodotoxin (TTX) and this could be due to a TXX-sensitive Na+ current. The expression of TTX-sensitive neuronal Nav1.1 and Nav1.2 isoforms has been reported in canine Purkinje myocytes. Our aim was to investigate by means of biochemical and functional techniques whether the TTX-sensitive skeletal Nav1.4 isoform is also expressed in canine cardiac Purkinje myocytes.Methods and Results: Using Nav1.4 specific primers, a PCR product corresponding to Nav1.4 was amplified from canine Purkinje fibers RNA and confirmed by sequencing and megablast of the gene bank. Confocal indirect immunostaining using anti-Nav1.4 antibody demonstrates distinct sarcolemmal staining pattern compared to that of the cardiac isoform Nav1.5. Expression of Nav1.4 in tsA201 cells yielded a TTX-sensitive Na+ current with an IC50 of 10 nM.Conclusions: These results demonstrate the expression of the TTX-sensitive Nav1.4 channel in canine cardiac Purkinje myocytes. This novel finding suggests a role of Nav1.4 channel in Purkinje myocytes and thus has important clinical implications for the mechanisms and management of ventricular arrhythmias originating in the Purkinje network. Published by Elsevier Inc.