Department of Physiology, IMB, University of Oslo, PB 1104 Blindern, 0317 Oslo, Norway.
J Physiol. 2014 Feb 15;592(4):669-93. doi: 10.1113/jphysiol.2013.267872. Epub 2013 Dec 23.
The dentate granule cells (DGCs) form the most numerous neuron population of the hippocampal memory system, and its gateway for cortical input. Yet, we have only limited knowledge of the intrinsic membrane properties that shape their responses. Since SK and Kv7/M potassium channels are key mechanisms of neuronal spiking and excitability control, afterhyperpolarizations (AHPs) and synaptic integration, we studied their functions in DGCs. The specific SK channel blockers apamin or scyllatoxin increased spike frequency (excitability), reduced early spike frequency adaptation, fully blocked the medium-duration AHP (mAHP) after a single spike or spike train, and increased postsynaptic EPSP summation after spiking, but had no effect on input resistance (Rinput) or spike threshold. In contrast, blockade of Kv7/M channels by XE991 increased Rinput, lowered the spike threshold, and increased excitability, postsynaptic EPSP summation, and EPSP-spike coupling, but only slightly reduced mAHP after spike trains (and not after single spikes). The SK and Kv7/M channel openers 1-EBIO and retigabine, respectively, had effects opposite to the blockers. Computational modelling reproduced many of these effects. We conclude that SK and Kv7/M channels have complementary roles in DGCs. These mechanisms may be important for the dentate network function, as CA3 neurons can be activated or inhibition recruited depending on DGC firing rate.
齿状回颗粒细胞(DGCs)是海马记忆系统中数量最多的神经元群体,也是皮质输入的门户。然而,我们对塑造其反应的内在膜特性只有有限的了解。由于 SK 和 Kv7/M 钾通道是神经元放电和兴奋性控制的关键机制,后超极化(AHP)和突触整合,我们研究了它们在 DGCs 中的功能。特定的 SK 通道阻滞剂 apamin 或 scyllatoxin 增加了尖峰频率(兴奋性),减少了早期尖峰频率适应,完全阻断了单个尖峰或尖峰序列后的中持续时间 AHP(mAHP),并增加了尖峰后的突触后 EPSP 总和,但对输入电阻(Rinput)或尖峰阈值没有影响。相比之下,XE991 阻断 Kv7/M 通道增加了 Rinput,降低了尖峰阈值,增加了兴奋性、突触后 EPSP 总和和 EPSP-尖峰耦合,但仅略微减少了尖峰序列后的 mAHP(而不是单个尖峰后的 mAHP)。SK 和 Kv7/M 通道的 opener 1-EBIO 和 retigabine 分别具有与阻滞剂相反的作用。计算模型再现了许多这些影响。我们得出结论,SK 和 Kv7/M 通道在 DGCs 中具有互补作用。这些机制对于齿状回网络功能可能很重要,因为 CA3 神经元可以根据 DGC 的放电率被激活或抑制。
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