Ca2+ sources for the exocytotic release of glutamate from astrocytes

Abstract

Astrocytes can exocytotically release the gliotransmitter glutamate from vesicular compartments. Increased cytosolic Ca2+ concentration is necessary and sufficient for this process. The predominant source of Ca2+ for exocytosis in astrocytes resides within the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate and ryanodine receptors of the ER provide a conduit for the release of Ca2+ to the cytosol. The ER store is (re)filled by the store-specific Ca2+-ATPase. Ultimately, the depleted ER is replenished by Ca2+ which enters from the extracellular space to the cytosol via store-operated Ca2+ entry; the TRPC1 protein has been implicated in this part of the astrocytic exocytotic process. Voltage-gated Ca2+ channels and plasma membrane Na+/Ca2+ exchangers are additional means for cytosolic Ca2+ entry. Cytosolic Ca2+ levels can be modulated by mitochondria, which can take up cytosolic Ca2+ via the Ca2+ uniporter and release Ca2+ into cytosol via the mitochondrial Na+/Ca2+ exchanger, as well as by the formation of the mitochondrial permeability transition pore. The interplay between various Ca2+ sources generates cytosolic Ca2+ dynamics that can drive Ca2+-dependent exocytotic release of glutamate from astrocytes. An understanding of this process in vivo will reveal some of the astrocytic functions in health and disease of the brain. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.