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 three mechanisms by which calcium pumps embedded in the cell-surface membrane are modulated. 1) Kinases are signaling proteins that regulate many cell processes. The possibility that a kinase called Lyk modulates calcium pumps will be tested. Lyk modulation of calcium pumps would identify a novel point of cross-talk between the kinase and calcium signaling pathways in nerve cells. 2) In response to toxic stimuli, calcium pumps move from cell-surface to intracellular membranes. The mechanism of pump trafficking will be determined to provide insight into how neurons adapt to stress. 3) Nerve cells express multiple genetic variants of calcium pumps. The possibility that certain variants specialize in regulating the calcium that triggers neurotransmitter release, the basis for chemical communication between neurons, will be examined. To achieve these goals, neurons will be grown in culture (in a dish) and studied individually with optical and electrophysiological instrumentation.

Carrying out this project in a university setting creates an environment for training scientists. Undergraduate and predoctoral students, postdoctoral trainees and faculty on sabbatical leave have all contributed to and will continue to participate in this research.

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.