Downregulation of KCC2 following LTP contributes to EPSP-spike potentiation in rat hippocampus.
Downregulation of KCC2 following LTP contributes to EPSP-spike potentiation in rat hippocampus.
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DOI：
10.1016/j.bbrc.2006.03.038
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发表时间：
2006-05
影响因子：
3.1
通讯作者：
Wei Wang;Neng Gong;Tian-Le Xu
中科院分区：
文献类型：
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作者：
Wei Wang;Neng Gong;Tian-Le Xu
GABA能突触抑制在调节突触传递和回路输出的长时程增强（LTP）过程中起着重要作用。K+-Cl−协同转运蛋白2（KCC 2）是决定抑制性GABA能突触强度的重要因素，除GABA A受体的贡献外。虽然已经获得了很多知识，在许多病理条件下的活性依赖性下调KCC 2，潜在的变化和贡献的KCC 2在LTP表达仍然是未知的。在本研究中，我们发现KCC 2的下调伴随着海马CA 1区LTP的发生，而不是长期抑郁的发生。同时，在Schaffer侧支突触LTP表达过程中，CA 3/DG及邻近皮质的KCC 2水平稳定。用APV阻断NMDA受体不仅阻止了LTP的诱导，而且也消除了KCC 2的减少。此外，速尿抑制KCC 2功能直接诱导EPSP峰电位（E-S）增强，这是海马LTP的重要组成部分。目前的数据表明，LTP的形成是伴随着KCC 2的下调，这是潜在的GABA能强度，最有可能有助于E-S增强LTP后的新机制。
GABAergic synaptic inhibition plays a critical role in regulating long-term potentiation (LTP) of glutamatergic synaptic transmission and circuit output. The K+–Cl−cotransporter 2 (KCC2) is an important factor in determining inhibitory GABAergic synaptic strength besides the contribution of GABAAreceptor. Although much knowledge has been gained regarding activity-dependent downregulation of KCC2 in many pathological conditions, the potential change and contribution of KCC2 in LTP expression is still unknown. In this study, we found that downregulation of KCC2 was accompanied with the occurrence of LTP but not that of long-term depression in hippocampal CA1 region. Meanwhile, KCC2 level in CA3/DG and adjacent cortex was stable in the process of LTP expression in Schaffer collateral synapses. Blockade of NMDA receptor with APV not only prevented LTP induction also abolished the reduction of KCC2. Furthermore, the inhibition of KCC2 function with furosemide directly induced EPSP–spike (E–S) potentiation, an important component of LTP in hippocampus. The present data suggest a novel mechanism that LTP formation is accompanied by the downregulation of KCC2, which is underlying GABAergic strength and most likely contributes to the E–S potentiation following LTP.