Biophysical properties of heteromultimeric erg K+ channels

Biophysical properties of heteromultimeric erg K+ channels
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异多聚体 erg K 通道的生物物理特性

DOI:
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发表时间:
2002
期刊:
Pflügers Archiv
影响因子:
--
通讯作者:
J. Schwarz
J. Schwarz
中科院分区:
--
文献类型:
--
作者:
S. Wimmers;C. Bauer;J. Schwarz

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抽象的。三个 ether-à-go-go 相关基因 (erg) K+ 通道亚基能够在其亚家族内​​形成异多聚体。原位杂交实验表明了这一发现的功能重要性,该实验表明不同的 erg 亚基在大脑的几个区域具有重叠的表达模式。为了研究异多聚体 erg 通道的生物物理特性,构建了两个 erg 亚基的串联体,并在中国仓鼠卵巢 (CHO) 细胞中异源表达。使用膜片钳技术测量产生的电流。与相应的野生型 (WT) erg 通道相比,异多聚体表现出中等的激活电位依赖性。相比之下,激活的时间过程显然由更快的激活亚基主导。所有异源多聚体的失活恢复动力学和失活动力学与 WT erg1 通道(人 erg1 K+ 通道 (HERG) 的大鼠同源物)相似,即使 erg1 不是多联体的一部分。总而言之,异多聚体 erg 通道的生物物理特性导致去极化和复极化时电流幅度更大。因此,通过异聚组装erg通道可以显着促进不同的生理功能,例如设置和稳定静息膜电位以及调节动作电位频率。
Abstract. The three ether-à-go-go-related gene (erg) K+ channel subunits are able to form heteromultimers within their subfamily. The functional importance of this finding is indicated by in situ hybridization experiments showing that the different erg subunits have overlapping expression patterns in several regions of the brain. To investigate the biophysical properties of heteromultimeric erg channels, concatemers of two erg subunits were constructed and expressed heterologously in Chinese hamster ovary (CHO) cells. The resulting currents were measured using the patch-clamp technique. The heteromultimers exhibited an intermediate potential dependence of activation compared with the corresponding wild-type (WT) erg channels. In contrast, the time course of activation was clearly dominated by the faster activating subunit. The kinetics of recovery from inactivation and the deactivation kinetics of all heteromultimers were similar to those of WT erg1 channels, the rat homologue of the human erg1 K+ channel (HERG), even if erg1 was not part of the concatemer. Taken together, the biophysical properties of heteromultimeric erg channels result in larger current amplitudes upon both depolarization and repolarization. Thus, through heteromeric assembly erg channels may contribute significantly to different physiological functions such as setting and stabilizing the resting membrane potential and modulation of action potential frequency.
DOI: 10.1152/jn.2000.83.3.1150
发表时间: 2000
影响因子: 2.5
作者:
Overholt,JL;Ficker,E;Yang,T;Shams,H;Bright,GR;Prabhakar,NR
通讯作者: Prabhakar,NR
DOI: 10.1073/pnas.91.8.3438
发表时间: 1994-04-12
影响因子: 11.1
作者:
WARMKE, JW;GANETZKY, B
通讯作者: GANETZKY, B