Zn2+ sensitivity of high- and low-voltage activated calcium channels
Zn2+ sensitivity of high- and low-voltage activated calcium channels
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DOI：
10.1529/biophysj.106.103333
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Feng, Zhong-Ping
中科院分区：
文献类型：
--
作者：
Sun, Hong-Shuo;Hui, Kwokyin;Feng, Zhong-Ping
必需阳离子锌（Zn 2+）阻断几种细胞类型中的电压依赖性钙通道，这些细胞类型对Zn 2+表现出不同的敏感性。Zn 2+对电压依赖性钙通道亚型作用的特异性尚未得到系统研究。在这项研究中，我们使用了一个瞬时蛋白表达系统，以确定Zn 2+对低压和高压激活通道的影响。我们发现在Ba ~（2+）中，Zn ~（2+）的IC_（50）值具有α（1）-亚基依赖性，Ca（V）1.2的IC_（50）值最低，Ca（V）3.1的IC_（50）值最高; Zn ~（21）通道对Zn ~（21）的敏感性大致为Ca（V）1.2> Ca（V）3.2> Ca（V）2.3> Ca（V）2.2 = Ca-V 2.1 >= Ca（V）3.3 = Ca（V）3.1。虽然Ca（V）2.2和Ca（V）3.1通道对Ba 2+中的Zn 2+具有相似的IC 50，但Ca（V）2.2而不是Ca（V）3.1通道对Ca 2+中的Zn 2+具有高10倍的IC 50。Ca（V）2.2通道对Ca ~（2+）中Zn ~（2+）的敏感性降低可通过破坏位于选择性外部的推定EF-手基序而部分逆转。筛选EEEE轨迹。因此，我们的研究结果支持的概念，Zn 2+块，介导的多种机制，可能取决于周围的α（1）孔区域的构象变化。这些.这些结果为锌对各种钙通道亚型的抑制作用机制提供了基本的见解。
The essential cation zinc (Zn2+) blocks voltage-dependent calcium channels in several cell types, which exhibit different sensitivities to Zn2+. The specificity of the Zn2+ effect on voltage-dependent calcium channel subtypes has not been systematically investigated. In this study, we used a transient protein expression system to determine the Zn2+ effect on lowand high-voltage activated channels. We found that in Ba2+, the IC50 value of Zn2+ was alpha(1)- subunit-dependent with lowest value for Ca(V)1.2, and highest for Ca(V)3.1; the sensitivity of the channels to Zn 21 was approximately ranked as Ca(V)1.2 > Ca(V)3.2 > Ca(V)2.3 > Ca(V)2.2 = Ca-V 2.1 >= Ca(V)3.3 = Ca(V)3.1. Although the Ca(V)2.2 and Ca(V)3.1 channels had similar IC50 for Zn2+ in Ba2+, the Ca(V)2.2, but not Ca(V)3.1 channels, had; 10- fold higher IC50 to Zn2+ in Ca2+. The reduced sensitivity of Ca(V)2.2 channels to Zn2+ in Ca2+ was partially reversed by disrupting a putative EF- hand motif located external to the selectivity. lter EEEE locus. Thus, our findings support the notion that the Zn2+ block, mediated by multiple mechanisms, may depend on conformational changes surrounding the alpha(1) pore regions. These. ndings provide fundamental insights into the mechanism underlying the inhibitory effect of zinc on various Ca2+ channel subtypes.