Vollum Institute, Oregon Health & Science University, Portland, Oregon, USA.
Nat Neurosci. 2011 Jun;14(6):744-9. doi: 10.1038/nn.2832. Epub 2011 May 22.
SK2-containing channels are expressed in the postsynaptic density (PSD) of dendritic spines on mouse hippocampal area CA1 pyramidal neurons and influence synaptic responses, plasticity and learning. The Sk2 gene (also known as Kcnn2) encodes two isoforms that differ only in the length of their N-terminal domains. SK2-long (SK2-L) and SK2-short (SK2-S) are coexpressed in CA1 pyramidal neurons and likely form heteromeric channels. In mice lacking SK2-L (SK2-S only mice), SK2-S-containing channels were expressed in the extrasynaptic membrane, but were excluded from the PSD. The SK channel contribution to excitatory postsynaptic potentials was absent in SK2-S only mice and was restored by SK2-L re-expression. Blocking SK channels increased the amount of long-term potentiation induced in area CA1 in slices from wild-type mice but had no effect in slices from SK2-S only mice. Furthermore, SK2-S only mice outperformed wild-type mice in the novel object recognition task. These results indicate that SK2-L directs synaptic SK2-containing channel expression and is important for normal synaptic signaling, plasticity and learning.
SK2 通道存在于树突棘突触后密度（PSD）中，可影响突触反应、可塑性和学习，这种通道在小鼠海马 CA1 锥体神经元中表达。Sk2 基因（也称为 Kcnn2）编码两种仅在其 N 端结构域长度上存在差异的同工型。SK2-长（SK2-L）和 SK2-短（SK2-S）在 CA1 锥体神经元中共表达，并可能形成异源二聚体通道。在缺乏 SK2-L（仅 SK2-S 小鼠）的小鼠中，SK2-S 通道存在于 extrasynaptic 膜中，但被排除在 PSD 之外。在仅 SK2-S 小鼠中，SK 通道对兴奋性突触后电位的贡献缺失，而通过重新表达 SK2-L 得以恢复。阻断 SK 通道增加了野生型小鼠切片中 CA1 区诱导的长时程增强的量，但在仅 SK2-S 小鼠切片中没有影响。此外，仅 SK2-S 小鼠在新物体识别任务中表现优于野生型小鼠。这些结果表明，SK2-L 指导突触 SK2 通道的表达，对正常的突触信号传递、可塑性和学习至关重要。
