Cellular mechanism for spontaneous calcium oscillations in astrocytes

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 mu mol/L thapsigargin, a blocker of sarcoplasmic reticulum Ca2+-ATPase; and 2) still robust after the application with either 50 mu mol/L ryanodine or 400 mu mol/L tetracaine, two specific antagonists of ryanodine receptors, but depressed in a dose-dependent manner by 2-APB, an InsP3 receptors (InsP(3)R) blocker. Conclusion: InsP(3)R-induced ER Ca2+ release is an important cellular mechanism for the initiation of spontaneous Ca2+ oscillation in hippocampal astrocytes.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000238485300013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Chemistry, MultidisciplinaryPharmacology & PharmacySCI(E)PubMed中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)13ARTICLE7861-8682