Synaptically induced sodium signals in hippocampal astrocytes in situ
Synaptically induced sodium signals in hippocampal astrocytes in situ
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DOI：
10.1113/jphysiol.2009.182279
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发表时间：
2009-12-15
影响因子：
5.5
通讯作者：
Rose, Christine R.
中科院分区：
文献类型：
--
作者：
Langer, Julia;Rose, Christine R.
星形胶质细胞与兴奋性突触紧密接触，并表达介导钠依赖性谷氨酸摄取的转运蛋白。在培养的星形胶质细胞中，选择性激活谷氨酸转运导致钠升高，刺激Na+/K+-ATP酶和葡萄糖摄取，表明谷氨酸的突触释放可能将兴奋性神经元活性与胶质细胞钠稳态和代谢偶联。在这里，我们分析了细胞内钠瞬变诱发的突触刺激急性小鼠海马脑片使用定量钠成像与钠敏感的荧光指示剂染料SBFI（钠结合苯并呋喃三甲酸酯）。我们发现，短爆发的谢弗侧支刺激引起钠瞬变在毫摩尔范围内的CA 1锥体神经元和SR 101阳性星形胶质细胞的放射层。在低刺激强度下，胶质细胞钠瞬变仅限于一到两个主要分支和相邻的细突起，只有微弱的侵入索马。通过增加刺激强度来增加激活的传入纤维的数量，引起在过程中以及星形胶质细胞的胞体中可检测到的全局钠瞬变。药理学分析表明，神经元钠信号主要归因于钠离子通过亲离子型谷氨酸受体内流。离子型受体的激活也有助于神经胶质细胞钠瞬变，而TBOA敏感的谷氨酸转运是负责钠流入星形胶质细胞的主要途径。因此，我们的研究结果表明，海马中的谷氨酸能突触传递导致星形胶质细胞中的钠瞬变，其主要由谷氨酸转运的激活介导。他们支持海马星形胶质细胞兴奋性突触活动、谷氨酸摄取和钠信号之间的联系。
Astrocytes are in close contact to excitatory synapses and express transporters which mediate the sodium-dependent uptake of glutamate. In cultured astrocytes, selective activation of glutamate transport results in sodium elevations which stimulate Na+/K+-ATPase and glucose uptake, indicating that synaptic release of glutamate might couple excitatory neuronal activity to glial sodium homeostasis and metabolism. Here, we analysed intracellular sodium transients evoked by synaptic stimulation in acute mouse hippocampal slices using quantitative sodium imaging with the sodium-sensitive fluorescent indicator dye SBFI (sodium-binding benzofuran isophthalate). We found that short bursts of Schaffer collateral stimulation evoke sodium transients in the millimolar range in both CA1 pyramidal neurons and in SR101-positive astrocytes of the stratum radiatum. At low stimulation intensities, glial sodium transients were confined to one to two primary branches and adjacent fine processes and only weakly invaded the soma. Increasing the number of activated afferent fibres by increasing the stimulation intensity elicited global sodium transients detectable in the processes as well as the somata of astrocytes. Pharmacological analysis revealed that neuronal sodium signals were mainly attributable to sodium influx through ionotropic glutamate receptors. Activation of ionotropic receptors also contributed to glial sodium transients, while TBOA-sensitive glutamate transport was the major pathway responsible for sodium influx into astrocytes. Our results thus establish that glutamatergic synaptic transmission in the hippocampus results in sodium transients in astrocytes that are mainly mediated by activation of glutamate transport. They support the proposed link between excitatory synaptic activity, glutamate uptake and sodium signals in astrocytes of the hippocampus.