Abstract
Aim:
To determine the Ca2+ source and cellular mechanisms of spontaneous Ca2+ oscillations in hippocampal astrocytes.
Methods:
The cultured cells were loaded with Fluo-4 AM, the indicator of intracellular Ca2+, and the dynamic Ca2+ transients were visualized with confocal laser-scanning microscopy.
Results:
The spontaneous Ca2+ oscillations in astrocytes were observed first in co-cultured hippocampal neurons and astrocytes. These oscillations were not affected by tetrodotoxin (TTX) treatment and kept up in purity cultured astrocytes. The spontaneous Ca2+ oscillations were not impacted after blocking the voltage-gated Ca2+ channels or ethylenediamine tetraacetic acid (EDTA) bathing, indicating that intracellular Ca2+ elevation was not the result of extracellular Ca2+ influx. Furthermore, the correlation between the spontaneous Ca2+ oscillations and the Ca2+ store in endoplasmic reticulum (ER) were investigated with pharmacological experiments. The oscillations were: 1) enhanced when cells were exposed to both low Na+ (70 mmol/L) and high Ca2+ (5 mmol/L) solution, and eliminated completely by 2 μmol/L thapsigargin, a blocker of sarcoplasmic reticulum Ca2+-ATPase; and 2) still robust after the application with either 50 μmol/L ryanodine or 400 μmol/L tetracaine, two specific antagonists of ryanodine receptors, but depressed in a dose-dependent manner by 2-APB, an InsP3 receptors (InsP3R) blocker.
Conclusion:
InsP3R-induced ER Ca2+ release is an important cellular mechanism for the initiation of spontaneous Ca2+ oscillation in hippocampal astrocytes.
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Project supported by National Natural Science Foundation of China (No 30421004, 30425035), State Key Basic Research Program of China (973, No 2004CB720007) and National Institutes of Health, USA (No NIH 5R01TW007269).
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Wang, Tf., Zhou, C., Tang, Ah. et al. Cellular mechanism for spontaneous calcium oscillations in astrocytes. Acta Pharmacol Sin 27, 861–868 (2006). https://doi.org/10.1111/j.1745-7254.2006.00397.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00397.x
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