Harrison N L, Radke H K, Tamkun M M, Lovinger D M
Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637.
Mol Pharmacol. 1993 Mar;43(3):482-6.
The actions of zinc ions on three species of K+ channels were studied using mouse fibroblasts stably transfected with a plasmid containing both the appropriate K+ channel gene and a steroid-inducible promotor. The channels studied were rKv1.1 and hKv1.5, delayed rectifiers cloned from rat and human tissue, respectively, and hKv1.4, an inactivating human K+ channel. Zn2+ shifted the activation curves for all three K+ currents in the depolarizing direction and also shifted the steady state inactivation curve for hKv1.4 in the depolarizing direction. The effect of Zn2+ was concentration dependent between 2 and 1000 microM. As a consequence of the modulation of gating, the activation kinetics of the K+ currents were slowed by Zn2+, an effect likely to delay repolarization of the neuronal action potential. The action of Zn2+ on these diverse K+ channels suggests the existence of a common Zn2+ binding domain, the occupation of which influences the voltage sensor. The resulting modulation of gating of hKv1.4 by Zn2+ may well be of physiological significance, in view of the localization of this channel in mossy fiber nerve terminals in the hippocampus, where Zn2+ is found in abundance.
利用稳定转染了包含合适的钾离子通道基因和类固醇诱导启动子的质粒的小鼠成纤维细胞，研究了锌离子对三种钾离子通道的作用。所研究的通道分别是rKv1.1和hKv1.5，它们是分别从大鼠和人类组织中克隆得到的延迟整流器，以及hKv1.4，一种失活的人类钾离子通道。锌离子使所有三种钾离子电流的激活曲线向去极化方向移动，并且也使hKv1.4的稳态失活曲线向去极化方向移动。在2至1000微摩尔之间，锌离子的作用呈浓度依赖性。作为门控调制的结果，锌离子使钾离子电流的激活动力学减慢，这种效应可能会延迟神经元动作电位的复极化。锌离子对这些不同的钾离子通道的作用表明存在一个共同的锌离子结合结构域，其占据会影响电压传感器。鉴于该通道在海马体苔藓纤维神经末梢中的定位（在那里发现大量锌离子），锌离子对hKv1.4门控的这种调制很可能具有生理意义。
