Single channel and ensemble hERG conductance measured in droplet bilayers.
Single channel and ensemble hERG conductance measured in droplet bilayers.
复制标题
在液滴双层中测量的单通道和整体 hERG 电导。
DOI：
10.1007/s10544-014-9919-4
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发表时间：
2015
影响因子：
2.8
通讯作者：
Schmidt,Jacob
中科院分区：
文献类型：
--
作者：
Vijayvergiya,Viksita;Acharya,Shiv;Poulos,Jason;Schmidt,Jacob
人类ether-a-go-go相关基因（hERG）编码钾通道Kv11.1，其在心脏动作电位中起关键作用，并与心脏疾病以及许多脱靶药物相互作用有关。该通道的电生理学主要使用膜片钳进行研究，但脂质双层具有提供一些优点的潜力，包括装置简单、易于使用以及控制膜和溶液组成的能力。我们从hERG表达细胞制备膜制剂，并使用液滴双层对其进行测量，允许测量通道集合电流和13.5 pS单通道电流。这些电流具有离子选择性，并可被E-4031和多非利特以剂量依赖性方式阻断，因此可以测定E-4031和多非利特的IC 50值分别为17 nM和9.65 μM。我们还观察到时间和电压依赖性电流的步骤变化后，在施加的电位，类似于以前报道的膜片钳测量。
The human ether-a-go-go related gene (hERG) encodes the potassium channel Kv11.1, which plays a key role in the cardiac action potential and has been implicated in cardiac disorders as well as a number of off-target pharmaceutical interactions. The electrophysiology of this channel has been predominantly studied using patch clamp, but lipid bilayers have the potential to offer some advantages, including apparatus simplicity, ease of use, and the ability to control the membrane and solution compositions. We made membrane preparations from hERG-expressing cells and measured them using droplet bilayers, allowing measurement of channel ensemble currents and 13.5 pS single channel currents. These currents were ion selective and were blockable by E-4031 and dofetilide in a dose-dependent manner, allowing determination of IC50values of 17 nM and 9.65 μM for E-4031 and dofetilide, respectively. We also observed time- and voltage- dependent currents following step changes in applied potential that were similar to previously reported patch clamp measurements.