SK2 channel plasticity contributes to LTP at Schaffer collateral-CA1 synapses
SK2 channel plasticity contributes to LTP at Schaffer collateral-CA1 synapses
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DOI：
10.1038/nn2041
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发表时间：
2008-02-01
影响因子：
25
通讯作者：
Maylie, James
中科院分区：
文献类型：
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作者：
Lin, Mike T.;Lujan, Rafael;Maylie, James
Schaffer侧支突触的突触强度的长时程增强（LTP）在很大程度上归因于AMPA受体（AMPAR）数量和生物物理性质的变化。小电导Ca2（+）激活的K+通道（SK2通道）在功能上与CA1棘中的NMDA受体（NMDAR）偶联，使得它们的活性调节兴奋性突触后电位（EPSP）的形状并增加诱导LTP的阈值。在这里，我们表明，在小鼠海马LTP诱导废除SK 2通道活动的增强突触。这种效应是由于SK2通道从突触后致密物（PSD）内化到脊柱中。阻断PKA或用代表SK2的C-末端结构域的肽进行细胞透析，所述肽含有三个已知的PKA磷酸化位点，阻断了LTP诱导后SK2通道的内化。因此，AMPAR的增加和SK 2通道的减少结合联合收割机产生了LTP基础上的EPSP增加。
Long-term potentiation (LTP) of synaptic strength at Schaffer collateral synapses has largely been attributed to changes in the number and biophysical properties of AMPA receptors (AMPARs). Small-conductance Ca2(+)-activated K+ channels (SK2 channels) are functionally coupled with NMDA receptors (NMDARs) in CA1 spines such that their activity modulates the shape of excitatory postsynaptic potentials (EPSPs) and increases the threshold for induction of LTP. Here we show that LTP induction in mouse hippocampus abolishes SK2 channel activity in the potentiated synapses. This effect is due to SK2 channel internalization from the postsynaptic density (PSD) into the spine. Blocking PKA or cell dialysis with a peptide representing the C-terminal domain of SK2 that contains three known PKA phosphorylation sites blocks the internalization of SK2 channels after LTP induction. Thus the increase in AMPARs and the decrease in SK2 channels combine to produce the increased EPSP underlying LTP.