The trinity of Ca2+ sources for the exocytotic glutamate release from astrocytes.
Astrocytes can exocytotically release the transmitter glutamate. Increased cytosolic Ca(2+) concentration is necessary and sufficient in this process. The source of Ca(2+) for the Ca(2+)-dependent exocytotic release of glutamate from astrocytes predominately comes from endoplasmic reticulum (ER) stores with contributions from both inositol 1,4,5-trisphosphate- and ryanodine/caffeine-sensitive stores. An additional source of Ca(2+) comes from the extracellular space via store-operated Ca(2+) entry due to the depletion of ER stores. Here transient receptor potential canonical type 1 containing channels permit entry of Ca(2+) to the cytosol, which can then be transported by the store-specific Ca(2+)-ATPase to (re)fill ER. Mitochondria can modulate cytosolic Ca(2+) levels by affecting two aspects of the cytosolic Ca(2+) kinetics in astrocytes. They play a role in immediate sequestration of Ca(2+) during the cytosolic Ca(2+) increase in stimulated astrocytes as a result of Ca(2+) entry into the cytosol from ER stores and/or extracellular space. As cytosolic Ca(2+)declines due to activity of pumps, such as the smooth ER Ca(2+)-ATPase, free Ca(2+) is slowly released by mitochondria into cytosol. Taken together, the trinity of Ca(2+) sources, ER, extracellular space and mitochondria, can vary concentration of cytosolic Ca(2+) which in turn can modulate Ca(2+)-dependent vesicular glutamate release from astrocytes. An understanding of how these Ca(2+) sources contribute to glutamate release in (patho)physiology of astrocytes will provide information on astrocytic functions in health and disease and may also open opportunities for medical intervention.
Reyes
Reno C
RC
Department of Neurobiology, Center for Glial Biology in Medicine, Atomic Force Microscopy & Nanotechnology Laboratories, Civitan International Research Center, Evelyn F McKnight Brain Institute, University of Alabama, Birmingham, AL 35294, United States.
Parpura
Vladimir
V
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D005110:Extracellular Space / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000502:physiology
D018698:Glutamic Acid; D002118:Calcium