Goldstein Steve An
Department of Biochemistry, Brandeis University, Waltham, MA, USA.
EMBO Mol Med. 2017 Apr;9(4):399-402. doi: 10.15252/emmm.201607479.
In this issue of , Decher (2017) identify a point mutation in the K2P2 (TREK‐1) potassium (K) channel that changes function in just those ways expected to predispose to right ventricular outflow tract (RVOT) ventricular tachycardia (VT) in the patient they study. Whereas wild‐type channels are selective for K and inhibited by β‐adrenergic stimulation, mutant I267T channels pass sodium (Na) into the cells, even during β‐adrenergic stimulation, and are more active in response to membrane stretch, changes predicted to enhance cardiac myocyte excitability. The report contributes to accumulating evidence for Na leak via K2P channels in association with normal development (Thomas , 2008), acquired arrhythmia (Ma , 2011), and now a missense mutation. Decher (2017) both inform and direct us toward interesting opportunities for further investigation.
在本期杂志中，德彻（2017年）在K2P2（TREK - 1）钾（K）通道中发现了一个点突变，其功能变化正是他们所研究的患者中预期易患右心室流出道（RVOT）室性心动过速（VT）的方式。野生型通道对K具有选择性，并受到β - 肾上腺素能刺激的抑制，而突变型I267T通道即使在β - 肾上腺素能刺激期间也会将钠（Na）转运到细胞中，并且对膜拉伸反应更活跃，这些变化预计会增强心肌细胞的兴奋性。该报告为通过K2P通道的钠泄漏与正常发育（托马斯，2008年）、获得性心律失常（马，2011年）以及现在的错义突变相关的证据积累做出了贡献。德彻（2017年）既为我们提供了信息，又引导我们走向进一步研究的有趣机会。
