β-amyloid increases dendritic Ca2+ influx by inhibiting the A-type K+ current in hippocampal CA1 pyramidal neurons
β-amyloid increases dendritic Ca2+ influx by inhibiting the A-type K+ current in hippocampal CA1 pyramidal neurons
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DOI：
10.1016/j.bbrc.2005.10.169
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发表时间：
2005-12-30
影响因子：
3.1
通讯作者：
Chen, C
中科院分区：
文献类型：
--
作者：
Chen, C
β-淀粉样肽（A β）的积累是阿尔茨海默病（AD）发病机制中的主要事件。然而，A β介导神经毒性并启动AD退行性过程的机制仍不清楚。最近的证据表明，电压门控性K+通道可能参与A β诱导的神经退行性过程。特别是，一个短暂的A型K+电流，其密度与从索马到远端树突在海马CA 1区锥体神经元的距离呈线性增加，已被证明有助于树突膜兴奋性。在这里，我报告说，A β（1-42）抑制树突状A型钾电流在海马CA 1区锥体神经元，这种抑制作用的原因增加反向传播树突状动作电位的幅度和相关的Ca 2+内流。这些结果表明，AD在树突状细胞中的沉积导致A型K+电流的持续抑制，将导致树突状细胞Ca（2+）内流的持续增加，并导致Ca（2+）稳态的丧失。这可能是导致突触失效并启动海马中神经元退行性过程的事件的组成部分。(c)2005年爱思唯尔公司All rights reserved.
Accumulation of the beta-amyloid peptide (A beta) is a primary event in the pathogenesis of Alzheimer's disease (AD). However, the mechanisms by which A beta mediates neurotoxicity and initiates the degenerative processes of AD are still not clear. Recent evidence shows that voltage-gated K+ channels may be involved in A beta-induced neurodegenerative processes. In particular, a transient A-type K+ current, with a linear increase in its density with distance from soma to distal dendrites in hippocampal CA1 pyramidal neurons, has been shown to contribute to dendritic membrane excitability. Here, I report that A beta (1-42) inhibits the dendritic A-type K+ current in hippocampal CA1 pyramidal neurons, and this inhibition causes increases in back-propagating dendritic action potential amplitude and associated Ca2+ influx. These results suggest that the persistent inhibition of the A-type K+ current resulting from deposition of AD in dendritic arborization will induce a sustained increase in dendritic Ca (2+) influx and lead to loss of Ca2+ homeostasis. This may be a component of the events that cause synaptic failure and initiate neuronal degenerative processes in the hippocampus. (c) 2005 Elsevier Inc. All rights reserved.