Department of Neuroscience, Cell Biology & Physiology, Wright State University, Boonshoft School of Medicine, Dayton, OH 45435, USA.
J Physiol. 2013 Feb 15;591(4):875-97. doi: 10.1113/jphysiol.2012.240879. Epub 2012 Nov 5.
Small-conductance calcium-activated potassium (SK) channels mediate medium after-hyperpolarization (AHP) conductances in neurons throughout the central nervous system. However, the expression profile and subcellular localization of different SK channel isoforms in lumbar spinal α-motoneurons (α-MNs) is unknown. Using immunohistochemical labelling of rat, mouse and cat spinal cord, we reveal a differential and overlapping expression of SK2 and SK3 isoforms across specific types of α-MNs. In rodents, SK2 is expressed in all α-MNs, whereas SK3 is expressed preferentially in small-diameter α-MNs; in cats, SK3 is expressed in all α-MNs. Function-specific expression of SK3 was explored using post hoc immunostaining of electrophysiologically characterized rat α-MNs in vivo. These studies revealed strong relationships between SK3 expression and medium AHP properties. Motoneurons with SK3-immunoreactivity exhibit significantly longer AHP half-decay times (24.67 vs. 11.02 ms) and greater AHP amplitudes (3.27 vs. 1.56 mV) than MNs lacking SK3-immunoreactivity. We conclude that the differential expression of SK isoforms in rat and mouse spinal cord may contribute to the range of medium AHP durations across specific MN functional types and may be a molecular factor distinguishing between slow- and fast-type α-MNs in rodents. Furthermore, our results show that SK2- and SK3-immunoreactivity is enriched in distinct postsynaptic domains that contain Kv2.1 channel clusters associated with cholinergic C-boutons on the soma and proximal dendrites of α-MNs. We suggest that this remarkably specific subcellular membrane localization of SK channels is likely to represent the basis for a cholinergic mechanism for effective regulation of channel function and cell excitability.
小电导钙激活钾 (SK) 通道在中枢神经系统中的神经元中介导中等后超极化 (AHP) 电导。然而，不同 SK 通道亚型在腰椎脊髓 α-运动神经元 (α-MN) 中的表达谱和亚细胞定位尚不清楚。通过对大鼠、小鼠和猫脊髓的免疫组织化学标记，我们揭示了 SK2 和 SK3 亚型在特定类型的 α-MN 中的差异和重叠表达。在啮齿动物中，SK2 在所有 α-MN 中表达，而 SK3 优先在小直径 α-MN 中表达；在猫中，SK3 在所有 α-MN 中表达。使用体内电生理特征鉴定的大鼠 α-MN 的事后免疫染色探索了 SK3 的功能特异性表达。这些研究揭示了 SK3 表达与中等 AHP 特性之间的强烈关系。具有 SK3-免疫反应性的运动神经元的 AHP 半衰减时间（24.67 与 11.02 毫秒）和 AHP 幅度（3.27 与 1.56 毫伏）明显长于缺乏 SK3-免疫反应性的 MN。我们得出结论，大鼠和小鼠脊髓中 SK 亚型的差异表达可能导致特定 MN 功能类型的中等 AHP 持续时间范围，并可能是区分啮齿动物中慢型和快型 α-MN 的分子因素。此外，我们的结果表明，SK2 和 SK3 免疫反应性富集在不同的突触后区域，其中包含与 α-MN 体和近端树突上的胆碱能 C-末梢相关的 Kv2.1 通道簇。我们认为，SK 通道这种非常特异的亚细胞膜定位可能代表了有效调节通道功能和细胞兴奋性的胆碱能机制的基础。
