Roncarati R, Di Chio M, Sava A, Terstappen G C, Fumagalli G
Department of Medicine and Public Health, Section of Pharmacology, University of Verona, 37134, Verona, Italy.
Neuroscience. 2001;104(1):253-62. doi: 10.1016/s0306-4522(01)00066-5.
Small conductance, calcium-activated potassium channels (SK channels) are present in most neurons, in denervated muscles and in several non-excitable cell types. In excitable cells SK channels play a fundamental role in the generation of the afterhyperpolarization which follows an action potential, thereby modulating neuronal firing and regulating excitability. To date, three channel subunits (SK1-3) have been cloned from mammalian brain. Since SK3 only has been shown to be expressed in muscles upon denervation, this channel may be involved in hyperexcitability and afterhyperpolarization observed in muscle cells in the absence of the nerve. Using confocal microscopy and SK3 specific antibodies, we demonstrate that SK3 immunoreactivity is present at the rat neuromuscular junction in denervated but also in innervated muscles. In denervated muscle fibers, SK3 is localized in the extrajunctional as well as the junctional plasma membrane, where it appears to be less abundant in the acetylcholine receptor-rich domains, corresponding to the crests of the postsynaptic folds. In innervated muscles, SK3 is not detectable in the muscle fiber but is present at the neuromuscular junction and seems to be localized presynaptically in the motor nerve terminals. Axonal accumulation of SK3 immunoreactivity occurs above and below a ligature of rat sciatic nerve, indicating that the SK3 protein is transported in both directions along the axons of the motor neurons. During rat development SK3 immunoreactivity is not found at the neuromuscular junction until day 35 of postnatal development when SK3 first appears in the motor neuron terminals. These results indicate that SK3 channels are components of the presynaptic compartment in the mature neuromuscular junction, where they may play an important regulatory role in synaptic transmission.
小电导钙激活钾通道（SK通道）存在于大多数神经元、失神经支配的肌肉以及几种非兴奋性细胞类型中。在可兴奋细胞中，SK通道在动作电位后的超极化后电位的产生中起基本作用，从而调节神经元放电并调节兴奋性。迄今为止，已从哺乳动物大脑中克隆出三种通道亚基（SK1 - 3）。由于仅显示SK3在失神经支配时在肌肉中表达，该通道可能参与了在无神经情况下肌肉细胞中观察到的过度兴奋和超极化后电位。使用共聚焦显微镜和SK3特异性抗体，我们证明SK3免疫反应性存在于大鼠失神经支配但也存在于有神经支配的肌肉的神经肌肉接头处。在失神经支配的肌纤维中，SK3定位于结外以及结区质膜，在富含乙酰胆碱受体的区域（对应于突触后褶皱的嵴）中其含量似乎较少。在有神经支配的肌肉中，在肌纤维中检测不到SK3，但存在于神经肌肉接头处，并且似乎定位于运动神经末梢的突触前。SK3免疫反应性在大鼠坐骨神经结扎上方和下方的轴突中积累，表明SK3蛋白沿运动神经元的轴突双向运输。在大鼠发育过程中，直到出生后第35天SK3首次出现在运动神经元末梢时，才在神经肌肉接头处发现SK3免疫反应性。这些结果表明，SK3通道是成熟神经肌肉接头突触前区室的组成部分，它们可能在突触传递中起重要的调节作用。
