Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ
Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ
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DOI：
10.1002/glia.21259
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发表时间：
2012-02-01
期刊：
影响因子：
6.2
通讯作者：
Rose, Christine R.
中科院分区：
文献类型：
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作者：
Langer, Julia;Stephan, Jonathan;Rose, Christine R.
在星形胶质细胞中，谷氨酸突触的激活主要是由钠依赖性谷氨酸摄取介导的长时间钠瞬变。钠升高激活星形胶质细胞的Na+/K+- atp酶和葡萄糖摄取，是神经胶质代谢与神经元活动耦合的关键信号。在这里，我们分析了钠信号在海马切片制备中星形胶质细胞之间的传播。对单个星形胶质细胞的刺激会导致钠离子立即升高，并在大约100 μ m的距离内扩散到邻近的星形胶质细胞。随着距离的增加，下游细胞中钠离子升高的幅度、斜率和传播速度单调衰减，表明存在扩散过程。与钠相比，电刺激引起的钙的增加仅限于受刺激的细胞和少数邻近的星形胶质细胞。药理抑制mGluR1/5可轻微抑制钠的扩散，而抑制谷氨酸摄取或嘌呤能受体则没有作用。在间隙连接的药理学抑制中，钠向邻近细胞的扩散受到干扰，在P4动物中减少，在Cx30/Cx43双缺陷小鼠中几乎没有。与之前在培养的星形胶质细胞中获得的结果相反，我们的数据表明，钙信号和代谢性谷氨酸受体支持（但不是先决条件）钠在海马星形胶质细胞间原位扩散，而Cx30和Cx43的表达是必不可少的。Cx30/ cx43介导的钠在星形胶质细胞间的扩散可能是一个信号，表明代谢需求增加，独立于伴随的钙信号。钠的扩散也可能通过支持陡峭的钠梯度的重建和降低单细胞的代谢负担而起稳态功能。(c) 2011 Wiley期刊公司
Activation of glutamatergic synapses results in long-lasting sodium transients in astrocytes mediated mainly by sodium-dependent glutamate uptake. Sodium elevations activate Na+/K+-ATPase and glucose uptake by astrocytes, representing key signals for coupling glial metabolism to neuronal activity. Here, we analyzed the spread of sodium signals between astrocytes in hippocampal slice preparations. Stimulation of a single astrocyte resulted in an immediate sodium elevation that spread to neighboring astrocytes within a distance of similar to 100 mu m. Amplitude, slope, and propagation speed of sodium elevations in downstream cells decayed monotonically with increasing distance, indicative of a diffusion process. In contrast to sodium, calcium increases elicited by electrical stimulation were restricted to the stimulated cell and a few neighboring astrocytes. Pharmacological inhibition of mGluR1/5 slightly dampened the spread of sodium, whereas inhibition of glutamate uptake or purinergic receptors had no effect. Spread of sodium to neighboring cells was disturbed on pharmacological inhibition of gap junctions, reduced in animals at P4 and virtually omitted in Cx30/Cx43 double-deficient mice. In contrast to results obtained earlier in cultured astrocytes, our data thus indicate that calcium signaling and metabotropic glutamate receptors are supportive of, but not prerequisites for, the spread of sodium between hippocampal astrocytes in situ, whereas expression of Cx30 and Cx43 is essential. Cx30/Cx43-mediated sodium diffusion between astrocytes could represent a signal indicating increased metabolic needs, independent of concomitant calcium signaling. Spread of sodium might also serve a homeostatic function by supporting the re-establishment of steep sodium gradients and by lowering the metabolic burden imposed on single cells. (c) 2011 Wiley Periodicals, Inc.