All ETDs from UAB

Advisory Committee Chair

Vladimir Parpura

Advisory Committee Members

Mathieu Lesort

Lori L McMahon-Wakefield

Harald W Sontheimer

Jacques Wadiche

Document Type

Dissertation

Date of Award

2009

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Astrocytes, a type of glial cell in the central nervous system, are recognized for their support roles to neurons. They supply neurons with metabolites, maintain ion homeostasis and clear the synaptic space of neurotransmitters. However, it has been found that some astrocytes have receptors for neurotransmitter and neuroligands, exhibit Ca2+ excitability when stimulated via these receptors, and secrete gliotransmitters as an output of this Ca2+ excitability. In the Ca2+-dependent release of glutamate, it has been shown that the endoplasmic reticulum is the predominant source and the extracellular space is the auxiliary source of free Ca2+ necessary for triggering exocytosis. Because astrocytes possess mitochondria and plasma membrane Ca2+ transport systems that play roles in Ca2+ signaling in other cell types including neurons, I hypothesized that these elements also regulate Ca2+ signaling in astrocytes, and can modulate glutamate release. Employing cultured astroctyes from the visual cortex of newborn rats, I measured changes in cytosolic Ca2+ in stimulated astrocytes, and in parallel experiments measured glutamate release through a glutamate dehydrogenase assay. I took a pharmacological approach to manipulate the Ca2+ handling of mitochondria and the plasma membrane Ca2+ transport systems. I showed that regulation of Ca2+ signaling by mitochondria and the plasma membrane Ca2+ transport systems correlates with modulation of glutamate release where an increase in cytosolic Ca2+ resulted in increase glutamate release. These studies expand what is known about Ca2+ signaling and exocytotic transmitter release in astrocytes. These studies may have medical relevance since the importance of Ca2+ signaling in astrocytes has been implicated in models of various neurological diseases.

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