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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+ current.
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Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+ current.

机译：钙调蛋白依赖性促进小脑P型Ca2 +电流的发育激活。

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摘要

P-type (CaV2.1) Ca2+ channels are a central conduit of neuronal Ca2+ entry, so their Ca2+ feedback regulation promises widespread neurobiological impact. Heterologous expression of recombinant CaV2.1 channels demonstrates that the Ca2+ sensor calmodulin can trigger Ca2+-dependent facilitation (CDF) of channel opening. This facilitation occurs when local Ca2+ influx through individual channels selectively activates the C-terminal lobe of calmodulin. In neurons, however, such calmodulin-mediated processes have yet to be detected, and CDF of native P-type current has thus far appeared different, arguably triggered by other Ca2+ sensing molecules. Here, in cerebellar Purkinje somata abundant with prototypic P-type channels, we find that the C-terminal lobe of calmodulin does produce CDF, and such facilitation augments Ca2+ entry during stimulation by repetitive action-potential and complex-spike waveforms. Beyond recapitulating key features of recombinant channels, these neurons exhibit an additional modulatory dimension: developmental upregulation of CDF during postnatal week 2. This phenomenon reflects increasing somatic expression of CaV2.1 splice variants that manifest CDF and progressive dendritic targeting of variants lacking CDF. Calmodulin-triggered facilitation is thus fundamental to native CaV2.1 and rapidly enhanced during early development.
机译：P型（CaV2.1）Ca2 +通道是神经元Ca2 +进入的中心管道，因此它们的Ca2 +反馈调节有望产生广泛的神经生物学影响。重组CaV2.1通道的异源表达表明Ca2 +传感器钙调蛋白可以触发通道开放的Ca2 +依赖性促进（CDF）。当通过各个通道的局部Ca2 +流入选择性激活钙调蛋白的C端叶时，就会发生这种促进作用。然而，在神经元中，尚未检测到这种钙调蛋白介导的过程，迄今为止，天然P型电流的CDF似乎有所不同，可以说是由其他Ca2 +传感分子触发的。在这里，在具有典型P型通道的小脑Purkinje躯体中，我们发现钙调蛋白的C末端波瓣确实会产生CDF，并且这种促进作用在Ca2 +进入过程中通过重复的动作电位和复杂的峰值波形增加。除了概括重组通道的关键特征外，这些神经元还显示了额外的调节维度：出生后第2周CDF发育上调。这种现象反映了CaV2.1剪接变体的体细胞表达增加，表现出CDF和对缺乏CDF的变体进行了树突状靶向。因此，钙调蛋白触发的促进作用是天然CaV2.1的基础，并在早期发育过程中迅速增强。

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