Agus Z S, Dukes I D, Morad M
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6085.
Am J Physiol. 1991 Aug;261(2 Pt 1):C310-8. doi: 10.1152/ajpcell.1991.261.2.C310.
The modulation of the transient outward K+ current (Ito) by divalent cations was studied in enzymatically isolated rat ventricular myocytes with the whole cell patch-clamp technique. At holding potentials negative to -70 mV, 1 mM Cd2+ suppressed Ito, whereas, at potentials positive to -50 mV, the current was augmented. These effects were caused by shifts in the voltage dependence of both activation and inactivation of Ito toward more positive potentials. Cd2+ also slowed the activation kinetics of Ito by shifting the voltage dependence of its rate of activation, but the rate of inactivation was unaffected. Other divalent cations produced similar shifts but at markedly different concentrations. Thus, in the millimolar range, a rightward shift of approximately 20 mV was produced by 3 Co2+, 5 Ni2+, and 10 Ca2+, whereas 10 microM concentrations of Cu2+ and Zn2+ produced equivalent shifts. Similar effects were seen in hippocampal neurons with micromolar concentrations of Zn2+. Thus divalent cations have marked and specific effects on the kinetics and voltage dependence of Ito and may serve as a regulatory mechanism in its activation, particularly in cells with resting potentials positive to -60 mV.
采用全细胞膜片钳技术，在酶分离的大鼠心室肌细胞中研究了二价阳离子对瞬时外向钾电流（Ito）的调节作用。在钳制电位负于 -70 mV时，1 mM Cd2+ 抑制Ito，而在电位正于 -50 mV时，电流增强。这些效应是由于Ito的激活和失活的电压依赖性均向更正的电位偏移所致。Cd2+ 还通过改变其激活速率的电压依赖性来减慢Ito的激活动力学，但失活速率不受影响。其他二价阳离子产生类似的偏移，但浓度明显不同。因此，在毫摩尔范围内，3 mM Co2+、5 mM Ni2+ 和10 mM Ca2+ 使电压依赖性向右偏移约20 mV，而10 μM浓度的Cu2+ 和Zn2+ 产生等效的偏移。在海马神经元中，微摩尔浓度的Zn2+ 也观察到类似的效应。因此，二价阳离子对Ito的动力学和电压依赖性具有显著且特异性的影响，并且可能在其激活过程中作为一种调节机制，特别是在静息电位正于 -60 mV的细胞中。
