Increased phosphorylation of the neuronal L-type Ca2+ channel Cav1.2 during aging
Increased phosphorylation of the neuronal L-type Ca2+ channel Cav1.2 during aging
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DOI：
10.1073/pnas.2236970100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Hell, JW
中科院分区：
文献类型：
--
作者：
Davare, MA;Hell, JW
通过l型Ca2+通道的Ca2+内流增加被认为是导致老年症状和阿尔茨海默病基础的神经元功能障碍的原因。神经元l型Ca2+通道活性的年龄依赖性上调的分子基础在很大程度上是未知的。我们发现，camp依赖性蛋白激酶对l型通道Ca(v)1.2的磷酸化在老年大鼠海马中增加了2倍。海马体对学习至关重要，是阿尔茨海默病中最先受到影响的大脑区域之一。camp依赖性蛋白激酶对Ca(v)1.2的磷酸化可显著增强其活性。因此，Ca(v)1.2磷酸化的增加可能是与年龄相关的神经元Ca2+内流升高及其神经病理后果的重要原因。
An increase in Ca2+ influx through L-type Ca2+ channels is thought to contribute to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease. The molecular basis of the age-dependent up-regulation in neuronal L-type Ca2+ channel activity is largely unknown. We show that phosphorylation of the L-type channel Ca(v)1.2 by cAMP-dependent protein kinase is increased >2-fold in the hippocampus of aged rats. The hippocampus is critical for learning and is one of the first brain regions to be affected in Alzheimer's disease. Phosphorylation of Ca(v)1.2 by cAMP-dependent protein kinase strongly enhances its activity. Therefore, increased Ca(v)1.2 phosphorylation may account for a substantial portion of the age-related rise in neuronal Ca2+ influx and its neuropathological consequences.