Ngo-Anh Thu Jennifer, Bloodgood Brenda L, Lin Michael, Sabatini Bernardo L, Maylie James, Adelman John P
Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Nat Neurosci. 2005 May;8(5):642-9. doi: 10.1038/nn1449. Epub 2005 Apr 24.
Small-conductance Ca(2+)-activated K(+) channels (SK channels) influence the induction of synaptic plasticity at hippocampal CA3-CA1 synapses. We find that in mice, SK channels are localized to dendritic spines, and their activity reduces the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent manner. Using combined two-photon laser scanning microscopy and two-photon laser uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca(2+) influx within individual spines. SK channels are tightly coupled to synaptically activated Ca(2+) sources, and their activity reduces the amplitude of NMDAR-dependent Ca(2+) transients. These effects are mediated by a feedback loop within the spine head; during an excitatory postsynaptic potential (EPSP), Ca(2+) influx opens SK channels that provide a local shunting current to reduce the EPSP and promote rapid Mg(2+) block of the NMDAR. Thus, blocking SK channels facilitates the induction of long-term potentiation by enhancing NMDAR-dependent Ca(2+) signals within dendritic spines.
小电导钙激活钾通道（SK通道）影响海马CA3-CA1突触处突触可塑性的诱导。我们发现，在小鼠中，SK通道定位于树突棘，并且它们的活性以N-甲基-D-天冬氨酸受体（NMDAR）依赖的方式降低诱发突触电位的幅度。通过结合双光子激光扫描显微镜和谷氨酸的双光子激光解笼，我们表明SK通道调节单个棘突内NMDAR依赖的Ca2+内流。SK通道与突触激活的Ca2+源紧密耦合，并且它们的活性降低NMDAR依赖的Ca2+瞬变的幅度。这些效应由棘突头部内的反馈回路介导；在兴奋性突触后电位（EPSP）期间，Ca2+内流打开SK通道，该通道提供局部分流电流以降低EPSP并促进NMDAR的快速Mg2+阻断。因此，阻断SK通道通过增强树突棘内NMDAR依赖的Ca2+信号来促进长时程增强的诱导。
