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.
