Modulation of Calcium Signaling in Neurons

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.