Astrocytes, a subtype of glial cell, exhibit a form of excitability based on intracellular Ca2+ variations. These intracellular calcium variations, i.e., oscillations can be evoked by neurotransmitters. The functional consequences of calcium oscillations in astrocytes are poorly understood. Since the level of intracellular calcium ions control glutamate release from astrocytes, we hypothesize that the frequency of calcium oscillations also control the amount of glutamate release from these cells. We will test this hypothesis in Specific Aim I. Calcium-dependent secretion in neurons can be modulated by the protein kinase A (PKA)- and protein kinase C (PKC)-dependent phosphorylation of secretory machinery downstream of calcium. Since astrocytes express the core proteins of the secretory machinery responsible for neuronal secretion, we hypothesize that glutamate release from astrocytes may also be modulated by PKA- and PKC-dependent phosphorylation at the site of secretory machinery. We will test this hypothesis in Specific Aim II. ? Specific Aim I: We will test the hypothesis that glutamate release from astrocytes is controlled by the frequency of calcium oscillations. ? Specific Aim Il: We will test the hypothesis that PKA and PKC modulate calcium-dependent glutamate release from astrocytes. ? This study will provide new and important information on how astrocytes communicate with neurons. Since astrocytes modulate synaptic transmission by releasing glutamate, this new insight into glial action has potential to change the way we think about central nervous system functions and dysfunctions ? ?
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