Mechanisms of glutamate release from astrocytes

Abstract

Astrocytes can release the excitatory transmitter glutamate which is capable of modulating activity in nearby neurons. This astrocytic glutamate release can occur through six known mechanisms: (i) reversal of uptake by glutamate (ii) anion channel opening induced by cell swelling, (iii) Ca 2+ -dependent exocytosis, (iv) glutamate exchange via the cystine-glutamate antiporter, (v) release through ionotropic purinergic receptors and (vi) functional unpaired connexons, 'hemichannels', on the cell surface. Although these various pathways have been defined, it is not clear how often and to what extent astrocytes employ different mechanisms. It will be necessary to determine whether the same glutamate release mechanisms that operate under physiological conditions operate during pathological conditions or whether there are specific release mechanisms that operate under particular conditions.

Loss of IP3Receptor-Dependent Ca2+Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

“…4 B). These findings are in agreement with the hypothesis that ambient glutamate release from astrocytes occurs in a Ca 2ϩ -independent manner, possibly through nonvesicular release mechanisms such as connexin hemichannels, P2X channels or anion channels (Cavelier and Attwell, 2005;Malarkey and Parpura, 2008).…”

Astrocytes and Epilepsy

“…46 Evidence of intracellular Ca 2ϩ release and Ca 2ϩ oscillations in NG2-like cells in the sclerotic focus, as argued for previously, along with evidence of the up-regulation of synaptosome associated protein 23 expression gathered from microarray analysis studies 50 suggest the possibility that in the sclerotic hippocampus are cells that may be capable of Ca 2ϩ -dependent exocytotic release of glutamate. 89 The intracellular Ca 2ϩ release pathway may be activated by the transcription factor NFkB, which is increased in the sclerotic hippocampus. 50,55 Experimental demonstration of the activation of the NFkB activated cycloxygenase-2/prostoglandin 2 mediated Ca 2ϩ release pathway in the human sclerotic hippocampus is still lacking.…”

Models of astrocytic Ca2+ dynamics and epilepsy

“…Hence, astrocytes exhibit Ca 2+ excitability in the form of Ca 2+ oscillations and intra-and inter-cellular waves in response to neuronal signals [5], since they express receptors for neurotransmitters and neuroligands [6]. Furthermore, astrocytic changes in intracellular Ca 2+ concentrations ([Ca 2+ ] i ) can result in Ca 2+ -dependent release of gliotransmitters such as glutamate [7]. In recent years, the Ca 2+ excitability of astrocytes, and their ability to release/uptake glutamate has implicated astrocytic role, not only in physiology, but also in pathophysiological states of the brain, including epilepsy [8].…”

“…Additionally, the protein function in astrocytes may be altered by culturing of these cells. For example, the purinergic P2X 7 receptor, an ATP-gated receptor channel, has been identified in dissociated culture, and, albeit with variable success, also in acute slices and in vivo. However, while its functionality has been confirmed in dissociated cultures of astrocytes, it seems to be absent in hippocampal astrocytes of rat and human acute slices [16].…”