Zhang Chao-Feng, Yang Pin
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.
Biochem Biophys Res Commun. 2006 Jun 23;345(1):43-9. doi: 10.1016/j.bbrc.2006.04.044. Epub 2006 Apr 24.
Zinc may play an important role in the pathogenesis of Alzheimer's disease (AD) through influencing the conformation and neurotoxicity of amyloid beta-proteins (Abeta). Zn(2+) induces rapid aggregation of synthetic or endogenous Abeta in a pH-dependent fashion. Here we show for the first time that Zn(2+)-induced aggregation of Abeta (10-21) potentiates its action on outward potassium currents in hippocampal CA1 pyramidal neurons. Using the whole-cell voltage-clamp technique, we showed that Abeta (10-21) blocked the fast-inactivating outward potassium current (I(A)) in a concentration- and aggregation-dependent manner, but with no effect on the delayed rectifier potassium current (I(K)). Both the unaggregated and aggregated forms of Abeta (10-21) significantly shifted the activation curve and the inactivation curve of I(A) to more negative potentials. But the aggregated form has more effects than the unaggregated form. These data indicated that aggregation of amyloid fragments by zinc ions is required in order to obtain full modulatory effects on potassium channel currents.
锌可能通过影响淀粉样β蛋白（Aβ）的构象和神经毒性在阿尔茨海默病（AD）的发病机制中发挥重要作用。锌离子（Zn(2+)）以pH依赖的方式诱导合成或内源性Aβ的快速聚集。在此，我们首次表明，Zn(2+)诱导的Aβ（10 - 21）聚集增强了其对海马CA1锥体神经元外向钾电流的作用。使用全细胞电压钳技术，我们发现Aβ（10 - 21）以浓度和聚集依赖的方式阻断快速失活的外向钾电流（I(A)），但对延迟整流钾电流（I(K)）无影响。未聚集和聚集形式的Aβ（10 - 21）均使I(A)的激活曲线和失活曲线显著向更负的电位移动。但聚集形式的影响比未聚集形式更大。这些数据表明，锌离子诱导淀粉样片段聚集是对钾通道电流获得完全调节作用所必需的。
