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首页> 外文期刊>Neurobiology of disease >Network excitability in a model of chronic temporal lobe epilepsy critically depends on SK channel-mediated AHP currents.
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Network excitability in a model of chronic temporal lobe epilepsy critically depends on SK channel-mediated AHP currents.

机译：慢性颞叶癫痫模型中的网络兴奋性严重取决于SK通道介导的AHP电流。

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摘要

Hippocampal CA1 pyramidal neurons generate an after-hyperpolarization (AHP) whose medium component is thought to be generated by small-conductance Ca(2+)-activated K(+) channels (SK channels). Neuronal excitability is increased in epilepsy, and the AHP in turn is fundamentally involved in regulation of cellular excitability. We therefore investigated the involvement of the SK channel-mediated AHP in controlling cell and network excitability in the pilocarpine model epilepsy. Both acutely isolated CA1 pyramidal cells and isolated hippocampal slices were investigated in terms of the impact of SK channel-mediated AHP on hyperexcitability. Our findings show that pilocarpine-treated chronically epileptic rats exhibit significantly reduced SK channel-mediated hyperpolarizing outward current which was accompanied by a significant decrease in the somatic AHP. Paradoxically, inhibiting SK channels strongly exacerbated 0-Mg(2+)-induced epileptiform activity in slices from pilocarpine-treated animals, while having a significantly smaller effect in control tissue. This suggests that in chronically epileptic tissue, network excitability very critically depends on the remaining SK-channel mediated AHP. Additional real-time RT-PCR and semiquantitative Western blot experiments revealed that both the SK2 channel transcript and protein were significantly downregulated in the epileptic CA1 region. We conclude that SK2 channels are down-regulated in chronic epilepsy underlying the impaired SK channel function in CA1 pyramidal cells, and a further reduction of the remaining critical mass of SK channels results in an acute network decompensation.
机译：海马CA1锥体神经元生成一个超极化后（AHP），其中等成分被认为是由小电导Ca（2+）激活的K（+）通道（SK通道）产生的。癫痫中神经元兴奋性增加，而AHP则从根本上参与细胞兴奋性的调节。因此，我们研究了毛果芸香碱模型癫痫中SK通道介导的AHP在控制细胞和网络兴奋性中的作用。就SK通道介导的AHP对过度兴奋性的影响而言，研究了急性分离的CA1锥体细胞和分离的海马切片。我们的发现表明，毛果芸香碱治疗的慢性癫痫大鼠表现出明显降低的SK通道介导的超极化外向电流，并伴随着体细胞AHP的显着降低。矛盾的是，抑制SK通道强烈增强了毛果芸香碱处理过的动物的切片中的0-Mg（2+）诱导的癫痫样活性，而在对照组织中的作用明显较小。这表明在慢性癫痫组织中，网络兴奋性非常关键地取决于剩余的SK通道介导的AHP。其他实时RT-PCR和半定量蛋白质印迹实验表明，癫痫CA1区的SK2通道转录物和蛋白质均显着下调。我们得出的结论是，在CA1锥体细胞中SK通道功能受损的慢性癫痫中，SK2通道被下调，而SK通道剩余临界质量的进一步降低导致急性网络失代偿。

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