Absence of a trafficking defect in R1232W/T1620M, a double SCN5A mutant responsible for Brugada syndrome
Absence of a trafficking defect in R1232W/T1620M, a double SCN5A mutant responsible for Brugada syndrome
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DOI：
10.1253/circj.72.1018
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Tsutsui, Hiroyuki
中科院分区：
文献类型：
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作者：
Makita, Naomasa;Mochizuki, Naoki;Tsutsui, Hiroyuki
背景Brugada综合征与突变型心脏Na通道（SCN 5A）的运输缺陷有关。尽管R1232 W多态性和T1620 M突变本身对Na通道功能的影响很小，但据报道，它们的组合破坏了膜运输，导致无功能的Na通道。方法和结果与以前的研究结果相反，异源表达的R1232 W/T1620 M的膜片钳记录显示了强大的Na电流，共聚焦显微镜显示主要表达在质膜上，结论SCN 5A的R1232 W和T1620 M之间的基因内相互作用不太可能导致运输缺陷导致无功能的Na通道。
Background A trafficking defect of mutant cardiac Na-channels (SCN5A) has been implicated in Brugada syndrome. Although R1232W polymorphism and T1620M mutation by themselves have little effect on Na-channel function, their combination has been reported to disrupt membrane trafficking, resulting in a non-functioning Na channel.Methods and Results Contrary to previous findings, patch-clamp recordings of heterologously expressed R1232W/T1620M showed robust Na currents and confocal microscopy exhibited predominant expression in the plasma membrane, similar to the wild-type channel.Conclusions It is unlikely that an intragenic interaction between R1232W and T1620M of SCN5A causes a trafficking defect leading to a non-functioning Na channel.