Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes.
Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes.
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DOI：
10.1042/an20110059
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发表时间：
2012-01-23
期刊：
影响因子：
4.7
通讯作者：
Parpura V
中科院分区：
文献类型：
--
作者：
Reyes RC;Verkhratsky A;Parpura V
星形胶质细胞兴奋性通过Ca 2 +cyt（胞质Ca 2+）的增加起作用，这可导致神经元能神经胶质传递。与此同时，星形胶质细胞Na+cyt（胞质Na+）的波动控制代谢神经元-神经胶质细胞信号传导，最显著的是通过刺激乳酸产生，乳酸从星形胶质细胞释放后可以被附近的神经元吸收和利用，这一过程称为乳酸穿梭。胶质传递和乳酸穿梭都在突触传递和可塑性的调节中发挥作用。因此，我们研究了PMCA（质膜Ca ~（2+）-ATP酶）、NCX（质膜Na ~+/Ca ~（2+）交换器）和NKA（Na ~+/K ~+-ATP酶）在星形胶质细胞静息和机械刺激时Ca ~（2+）cyt和Na ~+cyt复杂协调调节中的作用。我们的数据支持NKA和PMCA是静息星形胶质细胞中主要的Na+和Ca 2+挤出物的观点。令人惊讶的是，NKA或PMCA的阻断在机械刺激引起的Ca 2+和Na+胞质负荷期间显得不那么重要。出乎意料的是，NCX在反向模式下出现作为一个主要的贡献者整体钙和钠+稳态星形胶质细胞在休息时，这些胶质细胞受到机械刺激。此外，NCX促进机械诱导的钙依赖性谷氨酸从星形胶质细胞的胞吐释放。这些发现有助于更好地了解星形胶质细胞-神经元双向信号在三方突触和/或微血管。我们建议，NCX在反向模式下操作可能涉及快速和空间定位的Ca 2+依赖的gliotransmission，这将平行于一个更慢，更广泛分布的gliotransmission途径，需要代谢控制的Ca 2+释放从ER（内质网）。
Astroglial excitability operates through increases in Ca2+cyt (cytosolic Ca2+), which can lead to glutamatergic gliotransmission. In parallel fluctuations in astrocytic Na+cyt (cytosolic Na+) control metabolic neuronal-glial signalling, most notably through stimulation of lactate production, which on release from astrocytes can be taken up and utilized by nearby neurons, a process referred to as lactate shuttle. Both gliotransmission and lactate shuttle play a role in modulation of synaptic transmission and plasticity. Consequently, we studied the role of the PMCA (plasma membrane Ca2+-ATPase), NCX (plasma membrane Na+/Ca2+ exchanger) and NKA (Na+/K+-ATPase) in complex and coordinated regulation of Ca2+cyt and Na+cyt in astrocytes at rest and upon mechanical stimulation. Our data support the notion that NKA and PMCA are the major Na+ and Ca2+ extruders in resting astrocytes. Surprisingly, the blockade of NKA or PMCA appeared less important during times of Ca2+ and Na+ cytosolic loads caused by mechanical stimulation. Unexpectedly, NCX in reverse mode appeared as a major contributor to overall Ca2+ and Na+ homoeostasis in astrocytes both at rest and when these glial cells were mechanically stimulated. In addition, NCX facilitated mechanically induced Ca2+-dependent exocytotic release of glutamate from astrocytes. These findings help better understanding of astrocyte-neuron bidirectional signalling at the tripartite synapse and/or microvasculature. We propose that NCX operating in reverse mode could be involved in fast and spatially localized Ca2+-dependent gliotransmission, that would operate in parallel to a slower and more widely distributed gliotransmission pathway that requires metabotropically controlled Ca2+ release from the ER (endoplasmic reticulum).