RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; University of Nizhny Novgorod, Nizhny Novgorod 603022, Russia.
Cell Calcium. 2014 Feb;55(2):119-29. doi: 10.1016/j.ceca.2013.12.006. Epub 2014 Jan 8.
Astrocytes produce a complex repertoire of Ca2+ events that coordinate their major functions. The principle of Ca2+ events integration in astrocytes, however, is unknown. Here we analyze whole Ca2+ events, which were defined as spatiotemporally interconnected transient Ca2+ increases. Using such analysis in single hippocampal astrocytes in culture and in slices we found that spreads and durations of Ca2+ events follow power law distributions, a fingerprint of scale-free systems. A mathematical model demonstrated that such Ca2+ dynamics can arise from intracellular inositol-3-phosphate diffusion. The power law exponent (α) was decreased by activation of metabotropic glutamate receptors (mGluRs) either by specific receptor agonist or by low frequency stimulation of glutamatergic fibers in hippocampal slices. Decrease in α indicated an increase in proportion of large Ca2+ events. Notably, mGluRs activation did not increase the frequency of whole Ca2+ events. This result suggests that neuronal activity does not trigger new Ca2+ events in astrocytes (detectable by our methods), but modulates the properties of existing ones. Thus, our results provide a new perspective on how astrocyte responds to neuronal activity by changing its Ca2+ dynamics, which might further affect local network by triggering release of gliotransmitters and by modulating local blood flow.
星形胶质细胞产生一系列复杂的 Ca2+事件，这些事件协调着它们的主要功能。然而，星形胶质细胞中 Ca2+事件整合的原理尚不清楚。在这里，我们分析了全 Ca2+事件，这些事件被定义为时空上相互关联的瞬时 Ca2+增加。通过在培养的单个海马星形胶质细胞和切片中进行这种分析，我们发现 Ca2+事件的传播和持续时间遵循幂律分布，这是无标度系统的特征。一个数学模型表明，这种 Ca2+动力学可以源自细胞内肌醇-1,4,5-三磷酸扩散。通过使用特定的受体激动剂或通过低频刺激海马切片中的谷氨酸能纤维，代谢型谷氨酸受体 (mGluRs) 的激活会降低幂律指数 (α)。α 的降低表明大 Ca2+事件的比例增加。值得注意的是，mGluRs 的激活并没有增加全 Ca2+事件的频率。这一结果表明，神经元活动不会在星形胶质细胞中引发新的 Ca2+事件（通过我们的方法检测不到），而是调节现有 Ca2+事件的特性。因此，我们的结果提供了一个新的视角，即星形胶质细胞如何通过改变其 Ca2+动力学来响应神经元活动，这可能通过触发神经递质释放和调节局部血流来进一步影响局部网络。
