期刊
FRONTIERS IN CELLULAR NEUROSCIENCE
卷 4, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2010.00008
关键词
GABA; GABA receptors; stem cells; astrocyte; subventricular zone; neurogenesis; progenitor cells; proliferation
资金
- National Institute of Health [NS048256, DC007681]
- Yale Brown-Coxe fellowship
- NRSA [1F31NS063758-01A1]
In the adult neurogenic subventricular zone (SVZ), the behavior of astrocyte-like cells and some of their functions depend on changes in intracellular Ca2+ levels and tonic GABA(A) receptor activation. However, it is unknown whether, and if so how, GABA(A) receptor activity regulates intracellular Ca2+ dynamics in SVZ astrocytes. To monitor Ca2+ 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 Ca2+ increases in 40-50% of SVZ astrocytes. GABA(A)-induced Ca2+ increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC). The L- type Ca2+ 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 Ca2+ 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 Ca2+ dynamics through GABA(A) receptors and VGCC in a subpopulation of astrocyte-like cells in the postnatal SVZ.
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