Korvers Laura, de Andrade Costa Amanda, Mersch Martin, Matyash Vitali, Kettenmann Helmut, Semtner Marcus
Max-Delbrueck-Centrum for Molecular Medicine (MDC) in the Helmholtz Association, Cellular Neurosciences, Robert-Roessle-Str. 10, 13092 Berlin, Germany.
Max-Delbrueck-Centrum for Molecular Medicine (MDC) in the Helmholtz Association, Cellular Neurosciences, Robert-Roessle-Str. 10, 13092 Berlin, Germany.
Cell Calcium. 2016 Dec;60(6):396-406. doi: 10.1016/j.ceca.2016.09.004. Epub 2016 Sep 22.
Microglia are the resident immune cells in the central nervous system and many of their physiological functions are known to be linked to intracellular calcium (Ca) signaling. Here we show that isolated and purified mouse microglia-either freshly or cultured-display spontaneous and transient Ca elevations lasting for around ten to twenty seconds and occurring at frequencies of around five to ten events per hour and cell. The events were absent after depletion of internal Ca stores, by phospholipase C (PLC) inhibition or blockade of inositol-1,4,5-trisphosphate receptors (IPRs), but not by removal of extracellular Ca, indicating that Ca is released from endoplasmic reticulum intracellular stores. We furthermore provide evidence that autocrine ATP release and subsequent activation of purinergic P2Y receptors is not the trigger for these events. Spontaneous Ca transients did also occur after stimulation with Lipopolysaccharide (LPS) and in glioma-associated microglia, but their kinetics differed from control conditions. We hypothesize that spontaneous Ca transients reflect aspects of cellular homeostasis that are linked to regular and patho-physiological functions of microglia.
小胶质细胞是中枢神经系统中的常驻免疫细胞，已知它们的许多生理功能与细胞内钙（Ca）信号传导有关。在此我们表明，分离纯化的小鼠小胶质细胞——无论是新鲜的还是培养的——都会出现自发且短暂的钙升高，持续约十到二十秒，每小时每个细胞出现频率约为五到十次。在用磷脂酶C（PLC）抑制或阻断肌醇-1,4,5-三磷酸受体（IPR）耗尽细胞内钙储备后，这些事件消失，但去除细胞外钙则不会，这表明钙是从内质网细胞内储存中释放出来的。我们进一步提供证据表明，自分泌ATP释放及随后嘌呤能P2Y受体的激活不是这些事件的触发因素。在用脂多糖（LPS）刺激后以及在胶质瘤相关小胶质细胞中也会出现自发钙瞬变，但其动力学与对照条件不同。我们推测，自发钙瞬变反映了与小胶质细胞的正常和病理生理功能相关的细胞稳态方面。
