Differentiation of excitable cells and their evolution: role of potassium currents in regulating the electrical phenotype

脊椎动物的神经系统包含了种类繁多的神经细胞。每种类型的神经细胞都可以通过其形态、释放的化学物质、对化学物质的反应以及所显示的电活动模式来表征。这最后一个特性可以称为电表型。电活动有很广泛的分类，例如不能激发动作电位的神经细胞，那些只在膜上显示电压振荡的神经细胞，以及那些以爆发的方式激发的神经细胞。成熟的神经细胞由不可兴奋的干细胞发育而来，换句话说，它们不能在膜上产生电压变化。因此，在发育过程中，它们必须合成专门的蛋白质，即电压敏感的离子通道，以使它们具有电兴奋性。此外，由于不同类型的兴奋性存在差异，它们包含不同类型的通道（取决于哪些离子通过）和不同数量的通道。尽管电活动和新通道的合成之间似乎通过细胞内钙的水平存在反馈，但对调节这一过程的机制知之甚少。我们将使用来自最古老的多细胞动物群体水母的干细胞，来研究最早的动物在发育过程中如何改变神经细胞的兴奋性。重要的是要确定是否有一些古老的“规则”关于通道添加的顺序，以防止神经细胞进入非适应性甚至致命的中间兴奋状态。这些研究对于理解用于治疗帕金森病等疾病的移植祖神经细胞如何被说服分化出正确的电表型具有重要意义。

The vertebrate nervous system contains an amazing diversity of different types of nerve cells.  Each type of nerve cell can be characterized by its morphology, the chemicals that it releases, the chemicals it responds to, and the pattern of electrical activity that it displays.  This last property can be termed the electrical phenotype.  There are broad categories of electrical activity, for example nerve cells that cannot fire action potentials, those that only show voltage oscillations in their membrane, and those that fire in bursts.  Mature nerve cells develop from stem cells that are inexcitable, in other words they cannot generate voltage changes in their membranes.  Therefore, during development, they must synthesize specialized proteins, the voltage-sensitive ion channels, to give them electrical excitability.  Also, because there are differences in excitability from type to type they incorporate both different types of channels (depending on which ions pass through) and different numbers of channels. Very little is known about the mechanisms that regulate this process, though it seems that there is feedback between electrical activity and the synthesis of new channels through the levels of calcium in the cell.  We will use stem cells from the most ancient group of multi-celled animals, the jellyfish, to examine how the earliest animals alter the excitability of nerve cells during development. It is important to determine if there are some ancient "rules" about the order of channel addition to prevent nerve cells from passing through intermediate excitability states that are non-adaptive or even fatal to the cell.  These studies are important for understanding how implanted progenitor nerve cells, used for therapy of diseases such as Parkinson's, can be persuaded to differentiate the correct electrical phenotype.