Modulation of Calcium Signaling in Neurons

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Modulation of Calcium Signaling in NeuronsNerve cells convert electrical signals into changes in calcium ion to triggerbiochemical responses. Only during stimulation or under pathological conditionsare calcium levels elevated. Under normal conditions the intracellular calciumconcentration is kept very low by a complex series of pathways that pump calciumout of the cell or into organelles. The objective of this proposal is to study theregulation of three calcium regulatory processes. 1) Calcium is removed from thecell by pumps embedded in the cell-surface membrane. The mechanism by whicha particular genetic variation of the calcium pump is modulated by aneurotransmitter-activated pathway will be determined. 2) The mitochondrion isan intracellular organelle that participates in cellular energy metabolism and alsotakes up large amounts of calcium. The possibility that mitochondria act ascalcium sinks to create calcium microdomains will be examined. 3) When internalstores of calcium are depleted calcium influx pathways are activated to refill thestore. How this refilling pathway controls calcium release from the store will bedetermined. 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 rangingfrom gene expression to the release of neurotransmitters and hormones. Thus,fluctuations in calcium trigger adaptive changes in neurons and play an essentialrole in cell-to-cell communication. This work will increase our understanding ofhow neurons process information at the molecular and cellular level, and mayreveal new targets for drugs.