Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I
Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I
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DOI：
10.1523/jneurosci.0384-08.2008
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发表时间：
2008-06-04
影响因子：
5.3
通讯作者：
Derkach, Victor A.
中科院分区：
文献类型：
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作者：
Guire, Eric S.;Oh, Michael C.;Derkach, Victor A.
位于中枢神经元突触的Ca（2+）-可渗透AMPA受体（CP-AMPAR）由于其独特的生物物理和信号传导特性而引起人们的特别兴趣，这些特性有助于突触可塑性及其在多种神经病理学中的作用。然而，招募突触CP-AMPAR的细胞内信号传导途径是未知的，并且CP-AMPAR参与海马CA 1区突触可塑性是有争议的。在这里，我们报告说，细胞内灌注活性钙调素激酶I（CaMKI）到培养的海马神经元增强微型EPSC振幅，因为招聘的CP-AMPAR，可能从突触外池。调节肌动蛋白细胞骨架的CaMKI募集突触CP-AMPAR的能力通过用latrunculin A抑制肌动蛋白聚合来阻断。在海马切片中也证实了CP-AMPAR的CaMK调节。θ波爆发后的CA 1长时程增强（LTP），而不是高频强直，产生了快速，短暂的突触CP-AMPAR表达，促进LTP。TBS LTP的这一成分被CaMKI的上游激活剂CaM激酶激酶（CaMKK）的抑制所阻断。我们的计算表明，增加CP-AMPAR编号
Ca(2+)-permeable AMPA receptors (CP-AMPARs) at central glutamatergic synapses are of special interest because of their unique biophysical and signaling properties that contribute to synaptic plasticity and their roles in multiple neuropathologies. However, intracellular signaling pathways that recruit synaptic CP-AMPARs are unknown, and involvement of CP-AMPARs in hippocampal region CA1 synaptic plasticity is controversial. Here, we report that intracellular infusion of active CaM-kinase I (CaMKI) into cultured hippocampal neurons enhances miniature EPSC amplitude because of recruitment of CP-AMPARs, likely from an extrasynaptic pool. The ability of CaMKI, which regulates the actin cytoskeleton, to recruit synaptic CP-AMPARs was blocked by inhibiting actin polymerization with latrunculin A. CaMK regulation of CP-AMPARs was also confirmed in hippocampal slices. CA1 long-term potentiation (LTP) after theta bursts, but not high-frequency tetani, produced a rapid, transient expression of synaptic CP-AMPARs that facilitated LTP. This component of TBS LTP was blocked by inhibition of CaM-kinase kinase (CaMKK), the upstream activator of CaMKI. Our calculations show that adding CP-AMPARs numbering