Modulation of Calcium Signaling in Neurons

神经细胞钙信号的调节神经细胞将电信号转化为钙离子的变化，从而引发生物化学反应。只有在刺激或病理状态下，钙水平才会升高。在正常情况下，通过一系列复杂的途径将钙泵出细胞或进入细胞器，细胞内钙浓度保持在很低的水平。本提案的目的是研究三种钙调节过程的调节。1)钙通过嵌入细胞膜的泵从细胞中移除。钙泵的特定遗传变异是由神经递质激活途径调节的机制将被确定。2)线粒体是参与细胞能量代谢的胞内细胞器，同时也大量吸收钙。线粒体作为钙汇产生钙微域的可能性将被研究。3)当钙的内部储存被耗尽时，钙流入途径被激活以补充储存。这种再填充途径如何控制钙从储存中释放出来将被确定。为了实现这些目标，神经元将在培养皿中生长，并使用光学和电生理仪器单独研究。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过程。因此，钙的波动触发神经元的适应性变化，并在细胞间通讯中发挥重要作用。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，并可能揭示新的药物靶点。

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.