Cl⁻ homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses.
Cl⁻ homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses.
复制标题
DOI：
10.1113/jphysiol.2013.257162
复制
发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Fukuda A
中科院分区：
文献类型：
--
作者：
Egawa K;Yamada J;Furukawa T;Yanagawa Y;Fukuda A
gaba能信号从神经元传递到间隙连接偶联星形细胞网络的电生理特性和功能作用尚不清楚。gaba诱导的星形细胞Cl -通量被假设通过调节[Cl−]o来影响gaba能传输的驱动力。因此，揭示gaba介导的星形细胞反应的性质将加深我们对gaba能信号传递的理解。在这里，我们分析了CA1海马GABA能三方突触中神经元和星形胶质细胞的Cl -动力学，使用GABA应用期间的Cl -成像，以及空隙层-分子中神经元-星形胶质细胞对的全细胞记录。星形胶质细胞[Cl−]i调整到生理状态（40 mm）。虽然GABA在CA1星形胶质细胞中通过GABAA受体和小鼠GABA转运体4 （mGAT4）诱导了双向Cl -通量，但在相邻的星形胶质细胞中，一系列神经元间放电只诱导了GABAA受体介导的内向电流。GAT1抑制剂增加了神经元间的放电诱导电流，并诱导了双核蛋白不敏感的、mGAT4抑制剂敏感的电流，这表明GABA的突触外溢主要诱导了星形胶质细胞Cl -外溢，因为GABAA受体位于突触间隙附近。gaba诱导的Cl -外排伴随着Cl -虹吸通过星形胶质细胞网络的间隙连接，因为间隙连接抑制剂显著减少了神经元间放电诱导电流。因此，星形胶质细胞的Cl -外排在星形胶质细胞网络内得到稳态维持。一种间隙连接抑制剂增强了重复刺激gaba能突触引起的神经元多能干细胞逆转电位的活动依赖的去极化移动。这些结果表明星形细胞网络中的Cl -电导可能通过调节[Cl−]o来维持gaba能突触的传递。
The electrophysiological properties and functional role of GABAergic signal transmission from neurons to the gap junction-coupled astrocytic network are still unclear. GABA-induced astrocytic Cl− flux has been hypothesized to affect the driving force for GABAergic transmission by modulating [Cl−]o. Thus, revealing the properties of GABA-mediated astrocytic responses will deepen our understanding of GABAergic signal transmission. Here, we analysed the Cl− dynamics of neurons and astrocytes in CA1 hippocampal GABAergic tripartite synapses, using Cl− imaging during GABA application, and whole cell recordings from interneuron–astrocyte pairs in the stratum lacunosum-moleculare. Astrocytic [Cl−]i was adjusted to physiological conditions (40 mm). Although GABA application evoked bidirectional Cl− flux via GABAA receptors and mouse GABA transporter 4 (mGAT4) in CA1 astrocytes, a train of interneuron firing induced only GABAA receptor-mediated inward currents in an adjacent astrocyte. A GAT1 inhibitor increased the interneuron firing-induced currents and induced bicuculline-insensitive, mGAT4 inhibitor-sensitive currents, suggesting that synaptic spillover of GABA predominantly induced the astrocytic Cl− efflux because GABAA receptors are localized near the synaptic clefts. This GABA-induced Cl− efflux was accompanied by Cl− siphoning via the gap junctions of the astrocytic network because gap junction inhibitors significantly reduced the interneuron firing-induced currents. Thus, Cl− efflux from astrocytes is homeostatically maintained within astrocytic networks. A gap junction inhibitor enhanced the activity-dependent depolarizing shifts of reversal potential of neuronal IPSCs evoked by repetitive stimulation to GABAergic synapses. These results suggest that Cl− conductance within the astrocytic network may contribute to maintaining GABAergic synaptic transmission by regulating [Cl−]o.
登录
查看更多内容
影响因子：
4.2
作者：
Coyne, Leanne;Su, Jiping;Halliwell, Robert E.
通讯作者：
Halliwell, Robert E.
影响因子：
5.3
作者：
Banks, MI;Pearce, RA
通讯作者：
Pearce, RA
谷氨酸摄取触发转运蛋白介导的GABA从星形胶质细胞释放。
影响因子：
3.7
作者：
Héja L;Barabás P;Nyitrai G;Kékesi KA;Lasztóczi B;Toke O;Tárkányi G;Madsen K;Schousboe A;Dobolyi A;Palkovits M;Kardos J
通讯作者：
Kardos J
影响因子：
3.6
作者：
Krause, S;Schwarz, W
通讯作者：
Schwarz, W
影响因子：
6.2
作者：
Bekar, LK;Walz, W
通讯作者：
Walz, W