Electrophysiological Characteristics of a SCN5A Voltage Sensors Mutation R1629Q Associated With Brugada Syndrome

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	Electrophysiological Characteristics of a SCN5A Voltage Sensors Mutation R1629Q Associated With Brugada Syndrome
	Zeng, Zhipeng ; Zhou, Jieqiong ; Hou, Yuxi ; Liang, Xiaojing ; Zhang, Ziguan ; Xu, Xuejing ; Xie, Qiang ; Li, Weihua ; Huang, Zhengrong ; Zhou JQ(周洁琼) ; Liang XJ(梁晓静) ; Xie Q(谢强) ; Li WH(李卫华) ; Huang ZR(黄峥嵘)
刊名	http://dx.doi.org/10.1371/journal.pone.0078382
	2013
关键词	LONG QT SYNDROME SODIUM-CHANNEL DILATED CARDIOMYOPATHY MOTION ABNORMALITIES SLOW INACTIVATION DOMAIN IV CHANNELOPATHIES FIBRILLATION ACTIVATION MECHANISMS
英文摘要	Chinese National Science Foundation [81170090, 81270277]; Brugada syndrome (BrS) is an inherited arrhythmogenic syndrome leading to sudden cardiac death, partially associated with autosomal dominant mutations in SCN5A, which encodes the cardiac sodium channel alpha-subunit (Na(v)1.5). To date some SCN5A mutations related with BrS have been identified in voltage sensor of Na(v)1.5. Here, we describe a dominant missense mutation (R1629Q) localized in the fourth segment of domain IV region (DIV-S4) in a Chinese Han family. The mutation was identified by direct sequencing of SCN5A from the proband's DNA. Co-expression of Wild-type (WT) or R1629Q Na(v)1.5 channel and h beta 1 subunit were achieved in human embryonic kidney cells by transient transfection. Sodium currents were recorded using whole cell patch-clamp protocols. No significant changes between WT and R1629Q currents were observed in current density or steady-state activation. However, hyperpolarized shift of steady-state inactivation curve was identified in cells expressing R1629Q channel (WT: V-1/2 = -81.1 +/- 1.3 mV, n = 13; R1629Q: V-1/2 = -101.7 +/- 1.2 mV, n = 18). Moreover, R1629Q channel showed enhanced intermediate inactivation and prolonged recovery time from inactivation. In summary, this study reveals that R1629Q mutation causes a distinct loss-of-function of the channel due to alter its electrophysiological characteristics, and facilitates our understanding of biophysical mechanisms of BrS.
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93468]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Zeng, Zhipeng,Zhou, Jieqiong,Hou, Yuxi,et al. Electrophysiological Characteristics of a SCN5A Voltage Sensors Mutation R1629Q Associated With Brugada Syndrome[J]. http://dx.doi.org/10.1371/journal.pone.0078382,2013.
APA	Zeng, Zhipeng.,Zhou, Jieqiong.,Hou, Yuxi.,Liang, Xiaojing.,Zhang, Ziguan.,...&黄峥嵘.(2013).Electrophysiological Characteristics of a SCN5A Voltage Sensors Mutation R1629Q Associated With Brugada Syndrome.http://dx.doi.org/10.1371/journal.pone.0078382.
MLA	Zeng, Zhipeng,et al."Electrophysiological Characteristics of a SCN5A Voltage Sensors Mutation R1629Q Associated With Brugada Syndrome".http://dx.doi.org/10.1371/journal.pone.0078382 (2013).