Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Neurosci. 2013 Jan 16;33(3):1169-78. doi: 10.1523/JNEUROSCI.3920-12.2013.
Glia exhibit spontaneous and activity-dependent fluctuations in intracellular Ca(2+), yet it is unclear whether glial Ca(2+) oscillations are required during neuronal signaling. Somatic glial Ca(2+) waves are primarily mediated by the release of intracellular Ca(2+) stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca(2+) transients were identified in fine astrocytic processes and found to arise via an intracellular store-independent process. Here, we describe the identification of rapid, near-membrane Ca(2+) oscillations in Drosophila cortex glia of the CNS. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na(+)/Ca(2+), K(+) exchanger (zydeco) that is required for microdomain Ca(2+) oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to a variety of environmental stimuli, and that zydeco is required acutely in cortex glia to regulate seizure susceptibility. We also found that glial expression of calmodulin is required for stress-induced seizures in zydeco mutants, suggesting a Ca(2+)/calmodulin-dependent glial signaling pathway underlies glial-neuronal communication. These studies demonstrate that microdomain glial Ca(2+) oscillations require NCKX-mediated plasma membrane Ca(2+) flux, and that acute dysregulation of glial Ca(2+) signaling triggers seizures.
胶质细胞表现出细胞内 Ca(2+) 的自发和活动依赖性波动，但尚不清楚胶质细胞 Ca(2+) 振荡是否在神经元信号传递过程中是必需的。体细胞胶质细胞 Ca(2+) 波主要是通过细胞内 Ca(2+) 库的释放来介导的，其在正常大脑生理学中的相对重要性一直存在争议。最近，在细的星形胶质细胞突起中鉴定出了近膜微区 Ca(2+) 瞬变，并发现它们是通过一种不依赖于细胞内库的过程产生的。在这里，我们描述了在果蝇中枢神经系统皮层胶质细胞中快速、近膜 Ca(2+) 振荡的鉴定。在筛选温度敏感的条件性癫痫突变体时，我们鉴定出一种胶质特异性的 Na(+)/Ca(2+)、K(+) 交换体（zydeco），它是微区 Ca(2+) 振荡活性所必需的。我们发现，zydeco 突变体动物对各种环境刺激的癫痫易感性增加，并且 zydeco 在皮层胶质细胞中是急性需要的，以调节癫痫易感性。我们还发现，钙调蛋白在 zydeco 突变体的应激诱导性癫痫中是必需的，这表明 Ca(2+)/钙调蛋白依赖性胶质信号通路是胶质-神经元通讯的基础。这些研究表明，微区胶质细胞 Ca(2+) 振荡需要 NCKX 介导的质膜 Ca(2+) 流，并且胶质 Ca(2+) 信号的急性失调会引发癫痫。
