Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel
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DOI：
10.1113/jphysiol.1996.sp021410
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发表时间：
1996-06-15
影响因子：
5.5
通讯作者：
Heinemann, SH
中科院分区：
文献类型：
--
作者：
Schonherr, R;Heinemann, SH
1. 人类与鹰相关的钾离子通道HERG在非洲爪蟾卵母细胞中表达时，会产生向内整流的K+电流。明显的向内整流是由快速失活引起的。在细胞外Cs+溶液中，可以记录到大的向外电流，其失活时间常数为0 mV，约为50 ms，每37 mV变化e倍。HERG通道失活不是由氨基端球结构引起的，因为细胞质氨基端（HERG Delta 2-373）的缺失并没有消除失活。然而，在-80 mv时，通道失活速度加快了约12倍。S631突变为A，即HERG孔外口eag通道的同源残基，完全消除了通道失活。HERG通道的活性依赖于细胞外阳离子，细胞外阳离子对通道激活有效，Cs+>K（+）量级远大于Li+>Na+。点突变S631A强烈地减弱了这种通道的调节。通过类比克隆电压门控钾通道的功能方面，HERG的整流及其在动作电位过程中的动力学特性可能是由一种类似于c型失活的机制控制的。
1. The human eag-related potassium channel, HERG, gives rise to inwardly rectifying K+ currents when expressed in Xenopus oocytes.2. The apparent inward rectification is caused by rapid inactivation. In extracellular Cs+ solutions, large outward currents can be recorded having an inactivation time constant at 0 mV of about 50 ms with an e-fold change every 37 mV.3. HERG channel inactivation is not caused by an amino-terminal ball structure, as a deletion of the cytoplasmic amino terminus (HERG Delta 2-373) did not eliminate inactivation. However, channel deactivation was accelerated about 12-fold at -80 mV.4. Mutation of S631 to A, the homologous residue of eag channels, in the outer mouth of the HERG pore completely abolished channel inactivation.5. Activity of HERG channels depended on extracellular cations, which are effective for channel activation, in the order Cs+>K(+)much greater than Li+>Na+. The point mutation S631A strong ly reduced this channel regulation.6. By analogy to functional aspects of cloned voltage-gated potassium channels, rectification of HERG, as well as its kinetic properties during the course of an action potential, are presumably governed by a mechanism reminiscent of C-type inactivation.