Buffering Calcium Transients in Neurons

神经细胞利用钙离子将电信号转化为细胞内的生化变化。 电活动增加细胞内钙。 一旦进入细胞，钙就充当信使，将信息传递到细胞内部的各个部分。 仅在电刺激期间或在某些病理期间，细胞中的钙浓度升高。 在正常情况下，通过一系列复杂的途径将钙泵出细胞，细胞内钙浓度保持在很低的水平。 该项目的目标是表征从神经元中去除钙的过程。 主要目的是确定钙泵是如何被药物和环境因素调节的。 为实现这一目标，提出了四个具体目标。 1)将确定能量代谢改变对线粒体钙缓冲的影响。 2)钙泵家族的各种成员选择性地调节特定细胞功能的可能性将被探索。 3)将确定激素和神经递质对钙泵活性的影响。 4)一个专门的钙挤压蛋白定位于神经末梢的假设将被测试。 为了实现这些目标，神经元将在培养皿中生长，并使用研究者开发的光学和电生理仪器进行单独研究。 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。

Nerve cells employ calcium ions to convert electrical signals to biochemical changes within the cell. Electrical activity increases intracellular calcium. Once inside the cell, calcium acts as a messenger carrying information to various parts of the cell interior. Only during electrical stimulation, or during certain pathologies, is the calcium concentration in the cell elevated. Under normal conditions the intracellular calcium concentration is kept very low by a complex series of pathways which pump calcium out of the cell. The goal of this project is to characterize the processes which remove calcium from neurons. The principal objective is to determine how calcium pumps are modulated by drugs and environmental factors. Toward this objective 4 specific aims are proposed. 1) The effects of altered energy metabolism on calcium buffering by mitochondria will be determined. 2) The possibility that various members of the calcium pump family selectively regulate specific cell functions will be explored. 3) The effects of hormones and neurotransmitters on calcium pump activity will be determined. 4) The hypothesis that a specialized calcium extrusion protein is localized to nerve endings will be tested. To achieve these goals neurons will be grown in culture (in a dish), and studied individually employing optical and electrophysiological instrumentation developed by the investigator. This work will increase our understanding of how neurons process information at the molecular and cellular level, and may reveal new targets for drugs.