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惊人的不同类型的神经细胞的多样性。 每种类型的神经细胞都可以通过其形态，它释放的化学物质，它响应的化学物质以及它显示的电活动模式来表征。 这最后一个属性可以被称为电表型。 电活动有很大的类别，例如不能激发动作电位的神经细胞，那些只在膜中显示电压振荡的神经细胞，以及那些以突发方式激发的神经细胞。 成熟的神经细胞是从不可兴奋的干细胞发展而来的，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不同，它们包含不同类型的通道（取决于离子通过的通道）和不同数量的通道。关于调节这一过程的机制知之甚少，尽管似乎在电活动和通过细胞中钙水平合成新通道之间存在反馈。 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存在一些关于通道添加顺序的古老“规则”，以防止神经细胞通过对细胞来说是非适应性甚至是致命的中间兴奋性状态。 这些研究对于理解用于治疗帕金森病等疾病的植入祖神经细胞如何被说服分化正确的电表型非常重要。

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.