Departments of Neurosurgery and Cellular & Molecular Physiology, Yale University School of Medicine New Haven, CT, USA.
Front Cell Neurosci. 2010 Apr 8;4:8. doi: 10.3389/fncel.2010.00008. eCollection 2010.
In the adult neurogenic subventricular zone (SVZ), the behavior of astrocyte-like cells and some of their functions depend on changes in intracellular Ca(2+) levels and tonic GABA(A) receptor activation. However, it is unknown whether, and if so how, GABA(A) receptor activity regulates intracellular Ca(2+) dynamics in SVZ astrocytes. To monitor Ca(2+) activity selectively in astrocyte-like cells, we used two lines of transgenic mice expressing either GFP fused to a Gq-coupled receptor or DsRed under the human glial fibrillary acidic protein (hGFAP) promoter. GABA(A) receptor activation induced Ca(2+) increases in 40-50% of SVZ astrocytes. GABA(A)-induced Ca(2+) increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC). The L-type Ca(2+) channel activator BayK 8644 increased the percentage of GABA(A)-responding astrocyte-like cells to 75%, suggesting that the majority of SVZ astrocytes express functional VGCCs. SVZ astrocytes also displayed spontaneous Ca(2+) activity, the frequency of which was regulated by tonic GABA(A) receptor activation. These data support a role for ambient GABA in tonically regulating intracellular Ca(2+) dynamics through GABA(A) receptors and VGCC in a subpopulation of astrocyte-like cells in the postnatal SVZ.
在成年神经发生的侧脑室下区(SVZ)中,星形胶质细胞样细胞的行为及其部分功能取决于细胞内 Ca(2+)水平的变化和持续的 GABA(A)受体激活。然而,尚不清楚 GABA(A)受体活性是否以及如何调节 SVZ 星形胶质细胞内的 Ca(2+)动力学。为了选择性地监测星形胶质细胞样细胞中的 Ca(2+)活性,我们使用了两种表达 GFP 融合到 Gq 偶联受体或 DsRed 的转基因小鼠系,这些受体在人胶质纤维酸性蛋白(hGFAP)启动子下表达。GABA(A)受体的激活诱导了 40-50%的 SVZ 星形胶质细胞内的 Ca(2+)增加。Nifedipine 和 mibefradil (L 和 T 型电压门控钙通道(VGCC)的阻滞剂)可防止 GABA(A)诱导的 Ca(2+)增加。L 型钙通道激活剂 BayK 8644 将 GABA(A)反应性星形胶质细胞样细胞的比例提高到 75%,表明大多数 SVZ 星形胶质细胞表达功能性 VGCC。SVZ 星形胶质细胞还表现出自发的 Ca(2+)活动,其频率受持续的 GABA(A)受体激活调节。这些数据支持内源性 GABA 通过 GABA(A)受体和 VGCC 在 SVZ 中的星形胶质细胞样细胞亚群中持续调节细胞内 Ca(2+)动力学的作用。