CALCIUM INFLUX AND NEURODEGENERATION
CALCIUM INFLUX AND NEURODEGENERATION
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DOI：
10.1111/j.1749-6632.1993.tb18286.x
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发表时间：
1993-05-28
影响因子：
5.2
通讯作者：
MILLER, RJ
中科院分区：
文献类型：
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作者：
GIBBONS, SJ;BRORSON, JR;MILLER, RJ
Ca 2+跨神经元质膜的内流具有巨大的生理意义，因为细胞内游离Ca 2+浓度（[Ca 2 +] i）的增加与多种神经元过程相关。除了作为触发神经递质释放的基本信使外，CaZt还是控制神经元兴奋性、“电信号整合”、* 2各种类型的突触可塑性、3细胞代谢和基因表达的关键因素。所有的细胞内Ca 2+必须来自细胞外介质，尽管细胞内储存确实螯合Ca 2+并将其释放到细胞质中，当神经元在细胞外Ca 2+不存在的情况下孵育时，这允许[Ca 2 +] i升高。CaZt进入其电化学梯度是通过瞬时增加质膜对CaZt的渗透性来介导的。这可以通过打开CaZ+渗透性离子通道来实现，其中有两种主要类型：电压门控和配体门控。6-8电压门控Ca 2+通道通过膜电位的变化直接激活，而配体门控Ca 2+渗透性离子载体在神经递质与密切相关的受体结合后打开。6通过这两种途径的Ca 2+内流与各种形式的神经变性有关;然而，我们将在本文中讨论受体操纵的Ca 2+通道与神经元死亡的可能相关性。正如我们已经指出的，Ca 2+参与了许多与正常细胞功能相关的基本过程，并且[Ca 2 +] i通常受到密切调节。因此，[Caz+ Ii]的长期升高与延迟的细胞死亡直接相关可能并不奇怪。许多内源性和外源性化合物，包括兴奋性氨基酸神经递质受体激动剂和辣椒素（辣椒的辣味），都以这种Ca 2+依赖性方式导致细胞延迟死亡。此外，在一些病理条件下，如缺血、癫痫持续状态和创伤，
The influx of Ca2+ across the plasma membrane of neurons has enormous physiological significance because increases in the free intracellular CaZ+ concentration ([Ca2'Ii) are linked to a variety of neuronal processes. In addition to being the fundamental messenger as a trigger for neurotransmitter release, CaZt is a key element in the control of neuronal excitability,'integration of electrical signals,'* 2 synaptic plasticity of various types, 3 cellular metaboli~ m,~ and gene ex re~ sion.~ mately all intracellular Ca2+ must come from the extracellular medium, although intracellular stores do sequester CaZ+ and release it into the cytoplasm which permits rises in [Ca2+ Ii when neurons are incubated in the absence of extracellular Ca2+. The entry of CaZt down its electrochemical gradient is mediated by transiently increasing the permeability of the plasma membrane to CaZt. This can be achieved by opening CaZ+ permeable ion channels of which there are two principal types; voltage gated and ligand gated. 6-8 Voltage gated Ca2+ channels are directly activated by changes in the membrane potential whereas ligand gated Ca2+ permeable ionophores are opened following neurotransmitter binding to a closely associated receptor. 6 CaZ+ influx via both pathways has been implicated in various forms of neurodegeneration; however, it is the possible relevance of receptor operated Ca2+ channels to neuronal death which we shall discuss in this paper. As we have indicated, CaZ+ is involved in many fundamental processes relevant to normal cell function, and the [Ca2+ Ii s usually closely regulated. Therefore, it is perhaps not surprising that the prolonged elevation of [Caz+ Ii has been directly linked to delayed cell death. A number of endogenous and exogenous compounds including agonists for excitatory amino acid neurotransmitter receptors and capsaicin, the hot flavor of chili peppers, cause delayed cell death in just such a Ca2+-dependent manner. In addition, in several pathological conditions such as ischemia, status epilepticus and trauma, excessive intracellular accumulation of CaZt