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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Erg potassium currents of neonatal mouse purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation
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Erg potassium currents of neonatal mouse purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation

机译:新生小鼠浦肯野细胞的Erg钾电流表现出快速的门控动力学,并被mGluR1激活抑制

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We investigated the subthreshold properties of an erg (ether-à-go-go-related gene) K+ current in Purkinje cells of neonatal mice. Action potentials recorded from Purkinje cells in cerebellar slices exhibited a decreased threshold potential and increased frequency of spontaneous and repetitive activity following application of the specific erg channel blocker E-4031. Accommodation was absent before and after drug application. The erg current of these Purkinje cells activated at membrane potentials near -60 mV and exhibited fast gating kinetics. The functional importance of fast gating subthreshold erg channels in Purkinje cells was corroborated by comparing the results of action potential clamp experiments with erg1a, erg1b, erg2, and erg3 currents heterologously expressed in HEK cells. Computer simulations based on a NEURON model of Purkinje cells only reproduced the effects of the native erg current when an erg channel conductance like that of erg3 was included. Experiments with subunit-sensitive toxins (BeKm-1, APETx1) indicated that erg channels in Purkinje cells are presumably mediated by heteromeric erg1/erg3 or modified erg1 channels. Following mGluR1 activation, the native erg current was reduced by ~70%, brought about by reduction of the maximal erg current and a shift of the activation curve to more positive potentials. The Purkinje cell erg current contributed to the sustained current component of the biphasic mGluR1 response. Activation of mGluR1 by the agonist 3,4-dihydroxyphenylglycol increased Purkinje cell excitability, similar to that induced by E-4031. The results indicated that erg currents can be modulated and may contribute to the mGluR1-induced plasticity changes in Purkinje cells.
机译:我们调查了新生小鼠的Purkinje细胞中erg(与生命相关的基因)K +电流的亚阈值特性。在应用特定的erg通道阻滞剂E-4031后,小脑切片中Purkinje细胞记录的动作电位表现出降低的阈值电位以及自发性和重复性活动的频率增加。药物施用前后都没有住宿。这些浦肯野细胞的erg电流在接近-60 mV的膜电位下激活,并显示出快速的门控动力学。通过比较动作电位钳制实验与在HEK细胞中异源表达的erg1a,erg1b,erg2和erg3电流的结果,证实了快速门控亚阈erg通道在Purkinje细胞中的功能重要性。当包含诸如erg3的erg通道电导时,基于Purkinje细胞的NEURON模型的计算机模拟仅重现了自然erg电流的影响。亚基敏感毒素(BeKm-1,APETx1)的实验表明,Purkinje细胞中的erg通道大概是由异源erg1 / erg3或修饰的erg1通道介导的。在mGluR1激活后,天然erg电流降低了约70%,这是由于最大erg电流的降低以及激活曲线向更多正电位的移动所致。浦肯野细胞的erg电流促成了两相mGluR1反应的持续电流成分。激动剂3,4-二羟基苯基二醇对mGluR1的激活增加了Purkinje细胞的兴奋性,与E-4031诱导的类似。结果表明,erg电流可以被调制,并且可能有助于浦肯野细胞中mGluR1诱导的可塑性变化。

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