Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons
Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons
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DOI：
10.1073/pnas.97.15.8629
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发表时间：
2000-07-18
影响因子：
11.1
通讯作者：
Haydon, PG
中科院分区：
文献类型：
--
作者：
Parpura, V;Haydon, PG
星形胶质细胞可以以钙依赖的方式释放谷氨酸，从而向邻近的神经元发出信号。谷氨酸释放途径是否在生理信号传导过程中使用，或仅在病理生理条件下招募，尚未明确。缺乏理解的一个原因是对刺激星形胶质细胞释放谷氨酸所需的钙水平以及它们如何与这些细胞中的生理钙水平范围进行比较的知识有限。我们使用闪光光解提高星形胶质细胞的内部钙，同时监测星形胶质细胞的钙水平和谷氨酸，这引起了缓慢的内向电流，从星形胶质细胞微岛上生长的单个神经元记录电生理。通过这种方法，我们证明了星形胶质细胞钙的适度变化，从84到140 nM，在邻近神经元中引起大量的神经元能电流（-391 pA），希尔系数为2.1至2.7。因为激动剂谷氨酸，去甲肾上腺素。和多巴胺都将星形胶质细胞中的钙升高到超过1.8 μ M的水平，这些定量研究表明星形胶质细胞谷氨酸释放途径参与了内部钙的生理水平。因此，谷氨酸从星形胶质细胞的钙依赖性释放在星形胶质细胞钙水平的适当范围内起作用，以用作功能性神经系统内的信号传导途径。
Astrocytes can release glutamate in a calcium-dependent manner and consequently signal to adjacent neurons. Whether this glutamate release pathway is used during physiological signaling or is recruited only under pathophysiological conditions is not well defined. One reason for this lack of understanding is the limited knowledge about the levels of calcium necessary to stimulate glutamate release from astrocytes and about how they compare with the range of physiological calcium levels in these cells. We used flash photolysis to raise internal calcium in astrocytes, while monitoring astrocytic calcium levels and glutamate, which evoked slow inward currents that were recorded electrophysiologically from single neurons grown on microislands of astrocytes. With this approach, we demonstrate that modest changes of astrocytic calcium, from 84 to 140 nM, evoke substantial glutamatergic currents in neighboring neurons (-391 pA), with a Hill coefficient of 2.1 to 2.7. Because the agonists glutamate, norepinephrine. and dopamine all raise calcium in astrocytes to levels exceeding 1.8 mu M, these quantitative studies demonstrate that the astrocytic glutamate release pathway is engaged at physiological levels of internal calcium. Consequently, the calcium-dependent release of glutamate from astrocytes functions within an appropriate range of astrocytic calcium levels to be used as a signaling pathway within the functional nervous system.