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

可兴奋细胞的分化及其进化：钾电流在调节电表型中的作用

• 批准号: 419-2007
• 负责人: Spencer, Andrew
• 金额: $ 2.5万
• 依托单位: Vancouver Island University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=365794
• 关键词: Differentiation; excitable; cells; their; evolution

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.

脊椎动物的神经系统包含了各种不同类型的神经细胞。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。最后一种特性可以被称为电表型。有广泛的电活动类别，例如不能激发动作电位的神经细胞、仅在其膜中显示电压振荡的神经细胞以及以突发方式激发的神经细胞。成熟的神经细胞从不可兴奋的干细胞发育而来，换句话说，它们不能在其膜中产生电压变化。因此，在发育期间，它们必须合成特殊的蛋白质，即电压敏感离子通道，以赋予它们电兴奋性。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（取决于哪些离子通过）和不同数量的通道。我们对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内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有一些古老的“规则”关于通道添加的顺序，以防止神经细胞通过中间兴奋状态，是非适应性的，甚至是致命的细胞。这些研究是重要的，了解如何植入祖神经细胞，用于治疗疾病，如帕金森氏症，可以被说服分化正确的电表型。