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锌离子对培养的大鼠海马神经元电压门控钾电流的调节作用与Kv1.3通道无关。

The modulatory effect of zinc ions on voltage-gated potassium currents in cultured rat hippocampal neurons is not related to Kv1.3 channels.

作者信息

Teisseyre A, Mercik K, Mozrzymas J W

机构信息

Department of Biophysics, Wrocław Medical University, Wrocław, Poland.

出版信息

J Physiol Pharmacol. 2007 Dec;58(4):699-715.

PMID:18195482
Abstract

We applied the whole-cell patch-clamp technique to study the influence of zinc ions (Zn(2+)) and extracellular protons at acidic pH (pH(o)) on voltage-gated potassium currents in cultured rat hippocampal neurons. The first goal of the study was to estimate whether Kv1.3 currents significantly contributed to voltage-gated potassium currents in examined cells. Then, the influence of both ions on the activity of other voltage-gated potassium currents in the neurons was examined. We examined both the total current and the delayed - rectifier component. Results obtained in both cases were not significantly different from each other. Available data argued against any significant contribution of Kv1.3 currents to the recorded currents. Nevertheless, application of Zn(2+) in the concentration range from 100 microM to 5 mM reversibly modulated the recorded currents. The activation midpoint was shifted by about 40 mV (total current) and 30 mV (delayed-rectifier current) towards positive membrane potentials and the activation kinetics were slowed significantly (2 - 3 fold) upon application of Zn(2+). The inactivation midpoint was also shifted towards positive membrane potentials, but less significantly (about 14 mV). The current amplitudes were reduced in a concentration-dependent manner to about 0.5 of the control value. The effects of Zn(2+) were saturated at the concentration of 1 mM. Raising extracellular proton concentration by lowering the pH(o) from 7.35 to 6.4 did not affect significantly the currents. Possible mechanisms underlying the observed phenomena and their possible physiological significance are discussed.

摘要

我们应用全细胞膜片钳技术研究锌离子(Zn(2+))和酸性pH值(pH(o))下的细胞外质子对培养的大鼠海马神经元电压门控钾电流的影响。该研究的首要目标是评估Kv1.3电流是否对所检测细胞中的电压门控钾电流有显著贡献。然后,研究了这两种离子对神经元中其他电压门控钾电流活性的影响。我们检测了总电流和延迟整流成分。两种情况下获得的结果彼此之间无显著差异。现有数据表明Kv1.3电流对记录电流无显著贡献。然而,在100 microM至5 mM浓度范围内应用Zn(2+)可可逆地调节记录电流。施加Zn(2+)后,激活中点向正向膜电位移动约40 mV(总电流)和30 mV(延迟整流电流),激活动力学显著减慢(2至3倍)。失活中点也向正向膜电位移动,但幅度较小(约14 mV)。电流幅度以浓度依赖的方式降低至对照值的约0.5。Zn(2+)的作用在1 mM浓度时达到饱和。将pH(o)从7.35降低至6.4来提高细胞外质子浓度对电流无显著影响。文中讨论了所观察现象背后可能的机制及其可能的生理学意义。

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