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.
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http://dx.doi.org/10.1016/j.neuint.2008.12.018 | DOI Listing |
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Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
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Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
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Pediatric Orthopaedic Hospital, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710032, China.
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Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. Electronic address:
The development of a cytosolic delivery strategy for biopharmaceuticals is one of the central issues in drug development. Knowledge of the mechanisms underlying these processes may also pave the way for the discovery of novel delivery systems. L17E is a an attenuated cationic amphiphilic lytic (ACAL) peptide developed by our research group that shows promise for cytosolic antibody delivery.
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December 2024
School of Exercise and Nutritional Sciences, College of Health and Human Services, San Diego State University, 5500 Campanile Dr., San Diego, CA, 92182, USA.
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