Modulation of Calcium Signaling in Neurons

神经细胞中钙信号的调节神经细胞将电信号转化为钙离子的变化，从而触发生化反应。只有在刺激或病理条件下，钙水平才会升高。在正常情况下，细胞内的钙浓度通过一系列复杂的途径保持在非常低的水平，这些途径将钙泵出细胞或进入细胞器。这项建议的目的是研究三个钙调节过程的调控。1)通过嵌入细胞表面膜的泵将钙从细胞中排出。神经递质激活途径调节钙泵的特殊遗传变异的机制将被确定。2)线粒体是细胞内的细胞器，参与细胞的能量代谢，并摄取大量的钙。我们将研究线粒体作为钙离子下沉来创造钙微域的可能性。3)当体内储存的钙被耗尽时，钙流入途径被激活以补充储存。这个补充途径是如何控制钙从储藏室释放出来的，将会被确定。为了实现这些目标，神经元将在培养皿中培养，并使用光学和电生理仪器进行单独研究。钙作为细胞内信使，触发从基因表达到神经递质和激素释放的一系列过程。因此，钙离子的波动会触发神经元的适应性变化，并在细胞间的交流中发挥重要作用。这项工作将增加我们对神经元如何在分子和细胞水平上处理信息的理解，并可能揭示药物的新靶点。

Modulation of Calcium Signaling in NeuronsNerve cells convert electrical signals into changes in calcium ion to triggerbiochemical responses. Only during stimulation or under pathological conditionsare calcium levels elevated. Under normal conditions the intracellular calciumconcentration is kept very low by a complex series of pathways that pump calciumout of the cell or into organelles. The objective of this proposal is to study theregulation of three calcium regulatory processes. 1) Calcium is removed from thecell by pumps embedded in the cell-surface membrane. The mechanism by whicha particular genetic variation of the calcium pump is modulated by aneurotransmitter-activated pathway will be determined. 2) The mitochondrion isan intracellular organelle that participates in cellular energy metabolism and alsotakes up large amounts of calcium. The possibility that mitochondria act ascalcium sinks to create calcium microdomains will be examined. 3) When internalstores of calcium are depleted calcium influx pathways are activated to refill thestore. How this refilling pathway controls calcium release from the store will bedetermined. To achieve these goals neurons will be grown in culture (in a dish),and studied individually with optical and electrophysiological instrumentation.Calcium acts as an intracellular messenger that triggers processes rangingfrom gene expression to the release of neurotransmitters and hormones. Thus,fluctuations in calcium trigger adaptive changes in neurons and play an essentialrole in cell-to-cell communication. This work will increase our understanding ofhow neurons process information at the molecular and cellular level, and mayreveal new targets for drugs.