Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
J Neurosci. 2010 Sep 1;30(35):11726-34. doi: 10.1523/JNEUROSCI.1411-10.2010.
Small conductance Ca(2+)-activated K(+) type 2 (SK2) channels are expressed in the postsynaptic density of CA1 neurons where they are activated by synaptically evoked Ca(2+) influx to limit the size of EPSPs and spine Ca(2+) transients. At Schaffer collateral synapses, the induction of long-term potentiation (LTP) increases the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)-mediated contribution to synaptic transmission and decreases the synaptic SK2 channel contribution through protein kinase A-dependent channel endocytosis. Using a combination of electrophysiology and immunoelectron microscopy in mice, the relationship between the dynamics of spine SK2 channels and AMPARs was investigated. Unlike AMPARs, synaptic SK2 channels under basal conditions do not rapidly recycle. Furthermore, SK2 channels occupy a distinct population of endosomes separate from AMPARs. However, blocking vesicular exocytosis or the delivery of synaptic GluA1-containing AMPARs during the induction of LTP blocks SK2 channel endocytosis. By approximately 2 h after the induction of LTP, synaptic SK2 channel expression and function are restored. Thus, LTP-dependent endocytosis of SK2 is coupled to LTP-dependent AMPA exocytosis, and the approximately 2 h window after the induction of LTP during which synaptic SK2 activity is absent may be important for consolidating the later phases of LTP.
小电导钙激活钾通道 2 型（SK2）在 CA1 神经元的突触后密度中表达，在那里它们被突触诱发的 Ca2+内流激活，以限制 EPSP 和棘突 Ca2+瞬变的幅度。在 Schaffer 侧枝突触中，长时程增强（LTP）的诱导增加了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）对突触传递的贡献，并通过蛋白激酶 A 依赖性通道内吞作用降低了突触 SK2 通道的贡献。本研究在小鼠中结合使用电生理学和免疫电子显微镜技术，研究了棘突 SK2 通道和 AMPAR 之间的动态关系。与 AMPAR 不同，基础条件下的突触 SK2 通道不会快速循环。此外，SK2 通道占据了与 AMPAR 分离的内体的特定群体。然而，在 LTP 诱导期间阻断囊泡胞吐或突触 GluA1 包含的 AMPAR 的传递会阻止 SK2 通道内吞作用。在 LTP 诱导后约 2 小时，突触 SK2 通道的表达和功能得到恢复。因此，SK2 的 LTP 依赖性内吞作用与 LTP 依赖性 AMPA 胞吐作用偶联，并且在 LTP 诱导后大约 2 小时的时间窗口内，突触 SK2 活性缺失可能对巩固 LTP 的后期阶段很重要。
