Enhancement of K2P2.1 (TREK1) background currents expressed in Xenopus oocytes by voltage-gated K+ channel β subunits.
Enhancement of K2P2.1 (TREK1) background currents expressed in Xenopus oocytes by voltage-gated K+ channel β subunits.
复制标题
电压门控 K+ 通道 β 亚基增强非洲爪蟾卵母细胞中表达的 K2P2.1 (TREK1) 背景电流。
DOI：
10.1016/j.lfs.2012.08.011
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发表时间：
2012
期刊：
影响因子：
6.1
通讯作者：
Dierk Thomas
中科院分区：
文献类型：
--
作者：
J. Kisselbach;P. Schweizer;R. Gerstberger;R. Becker;H. Katus;Dierk Thomas
AIMSK2P2.1(TREK1)双孔结构域钾通道控制中枢神经系统(CNS)和心脏的电活动。辅助β亚基(Kvβ)增加中枢功能性K+通道的多样性。基于Kvβ2蛋白和K2P2.1通道在神经元兴奋性中的相似组织分布和共同的功能意义，我们假设Kvβ2亚基调节K2P2.1电流。主要方法在非洲爪哇卵母细胞中表达K2P2.1通道和rKvβ亚基，并用双电极电压钳电生理方法评估K2P2.1的功能。KEY FINDINGSKVβ2亚基以浓度依赖的方式使K2P2.1电流增加2.9倍(I0 mV，K2P2.1，0.53±0.07μA；I0mV，K2P2.1+Kvβ2，1.56±0.13μ；n=15)。刺激K2P2.1通道可引起静息膜电位超极化，−为10.7 mV(n=15)。与Kvβ2共表达后，K2P2.1通道的开放整流和电流-电压关系无明显改变，K2P2.1膜表达不受Kvβ2亚单位的影响。相关亚基Kvβ1(1.7倍；n=16)、Kvβ3(2.2倍；n=16)和Kvβ4(2.8倍；n=16)类似地激活K2P2.1电流，表明Kvβ蛋白在K2P2.1调节中发挥更广泛的作用。Kvβ亚基通过增强K2P2.1K+电流来稳定静息膜电位。这一以前未被认识的生物物理机制在神经生理学中的意义仍有待研究。
AIMSK2P2.1 (TREK1) two-pore-domain potassium channels control electrical activity in the central nervous system (CNS) and in the heart. Auxiliary β subunits (Kvβ) increase functional K+channel diversity in the CNS. Based on similar tissue distribution and common functional significance of Kvβ2 protein and K2P2.1 channels in neuronal excitability, we hypothesized that Kvβ2 subunits modulate K2P2.1 currents.MAIN METHODSRat K2P2.1 channels and rKvβ subunits were expressed in Xenopus laevis oocytes, and two-electrode voltage clamp electrophysiology was used to assess K2P2.1 function.KEY FINDINGSKvβ2 subunits increased K2P2.1 currents by 2.9‐fold in concentration-dependent fashion (I0mV,K2P2.1, 0.53±0.07μA; I0mV,K2P2.1+Kvβ2, 1.56±0.13μA; n=15). K2P2.1 channel stimulation resulted in resting membrane potential hyperpolarization by −10.7mV (n=15). Open rectification and current-voltage relationships of K2P2.1 channels were not markedly altered upon co-expression with Kvβ2, and K2P2.1 membrane expression was not affected by Kvβ2 subunits. Related subunits Kvβ1 (1.7-fold; n=16), Kvβ3 (2.2-fold; n=16), and Kvβ4 (2.8-fold; n=16) similarly activated K2P2.1 currents, indicating a broader role for Kvβ proteins in K2P2.1 regulation.SIGNIFICANCEKvβ subunits stabilize the resting membrane potential through enhancement of K2P2.1K+currents. The significance of this previously unappreciated biophysical mechanism in neuronal physiology remains to be investigated.