Is Version Of
This dissertation deals with release of neurotransmitter from glia. It has been demonstrated that bradykinin causes a receptor-mediated release of excitatory amino acids (EAAs), glutamate and aspartate, from glial cultures obtained from dorsal root ganglia (DRG) together with an increase in the cytoplasmic level of glial free calcium. Perturbations which inhibited bradykinin-induced calcium mobilization prevented the release of EAAs from glia. The addition of ionomycin caused a calcium-dependent release of EAAs. Taken together, these data demonstrate that calcium is both necessary and sufficient for stimulating the release of EAAs from DRG glia;Bradykinin was applied to mixed neuron-glial cultures derived from rat cerebral cortex while monitoring calcium levels. Bradykinin elevated calcium levels in neurons only when neurons contacted glia. The general glutamate receptor antagonist, D-glutamylglycine (DGG), prevented bradykinin-induced neuronal calcium elevation. These data indicate that bradykinin elevates neuronal calcium levels through the action of glutamate that is released from glia. While addition of bradykinin to mixed neuron-glial culture is the simplest experimental method of testing the hypothesis that glia can signal to neurons, a second technique allowed a more direct test of this hypothesis. Direct photo-stimulation of glia was used to increase glial calcium levels. A portion of glia was exposed to focal application of UV light while monitoring the calcium response. Photo-stimulation reliably raised the level of calcium in the glial cell. Since elevated calcium is sufficient to stimulate the release of glutamate from glia, this perturbation induced the calcium-dependent release of glutamate. By monitoring calcium levels from adjacent neurons, it was possible to determine that photo-stimulation of glia caused an elevation in calcium levels of adjacent unstimulated neurons. This effect was greatly reduced by DGG. Thus, glia can regulate neuronal calcium levels through glutamate-mediated actions.