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首页> 外文期刊>Cellular Physiology and Biochemistry >Biophysical Characterization of the Short QT Mutation hERG-N588K Reveals a Mixed Gain-and Loss-of-Function
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Biophysical Characterization of the Short QT Mutation hERG-N588K Reveals a Mixed Gain-and Loss-of-Function

机译：短QT突变hERG-N588K的生物物理特征揭示了混合的获得和失去功能

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摘要

The short QT syndrome is a newly discovered pro-arrhythmic condition, which may cause ventricular fibrillation and sudden death. Short QT can originate from the apparent gain-of-function mutation N588K in the hERG potassium channel that conducts repolarising I-Kr current. The present study describes a profound biophysical characterization of HERG-N588K revealing both loss-of-function and gain-of-function properties of the mutant. Experiments were conducted after heterologous expression in both Xenopus laevis oocytes and mammalian cells and at both room temperature and at 37 C. Also the impact of the beta-subunits KCNE2 was investigated. The most prominent loss-of-function property of HERG-N588K was reduced tail currents but also the activation properties was compromised. Based on these biophysical results we suggest that the general view of HERG-N588K being a gain-of-function is modified to a mixed gain-and loss-of-function mutation. This might also have impact on the pathological picture of the HERG-N588K channels ability to trigger arrhythmic events.
机译：短QT综合征是一种新发现的心律失常，可能导致心室纤颤和猝死。短QT可能源自hERG钾通道中明显的功能获得突变N588K，该突变传导I-Kr电流复极化。本研究描述了HERG-N588K的深刻生物物理特征，揭示了突变体的功能丧失和功能获得特性。在非洲爪蟾卵母细胞和哺乳动物细胞中以及在室温和37℃下异源表达后进行实验。还研究了β亚基KCNE2的影响。 HERG-N588K最突出的功能丧失特性是降低尾电流，但其激活特性也受到损害。基于这些生物物理结果，我们建议将HERG-N588K作为一种功能获得的一般观点被修改为一种混合的功能获得和功能丧失突变。这也可能对HERG-N588K通道触发心律不齐事件的能力的病理学影响。

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