Modulation of Calcium Signaling in Neurons

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

Modulation of Calcium Signaling in Neurons Nerve cells convert electrical signals into changes in calcium ion to trigger biochemical responses. Only during stimulation or under pathological conditions are calcium levels elevated. Under normal conditions the intracellular calcium concentration is kept very low by a complex series of pathways that pump calcium out of the cell or into organelles. The objective of this proposal is to study the regulation of three calcium regulatory processes. 1) Calcium is removed from the cell by pumps embedded in the cell-surface membrane. The mechanism by which a particular genetic variation of the calcium pump is modulated by a neurotransmitter-activated pathway will be determined. 2) The mitochondrion is an intracellular organelle that participates in cellular energy metabolism and also takes up large amounts of calcium. The possibility that mitochondria act as calcium sinks to create calcium microdomains will be examined. 3) When internal stores of calcium are depleted calcium influx pathways are activated to refill the store. How this refilling pathway controls calcium release from the store will be determined. 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 ranging from gene expression to the release of neurotransmitters and hormones. Thus, fluctuations in calcium trigger adaptive changes in neurons and play an essential role in cell-to-cell communication. This work will increase our understanding of how neurons process information at the molecular and cellular level, and may reveal new targets for drugs.