Ryanodine receptor- and sodium-calcium exchanger-mediated spontaneous calcium activity in immature oligodendrocytes in cultures
Ryanodine receptor- and sodium-calcium exchanger-mediated spontaneous calcium activity in immature oligodendrocytes in cultures
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DOI：
10.1016/j.neulet.2020.134913
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发表时间：
2020-07-27
影响因子：
2.5
通讯作者：
Kirischuk, Sergei
中科院分区：
文献类型：
--
作者：
Bassetti, Davide;Hammann, Jens;Kirischuk, Sergei
中枢神经系统中的髓鞘形成依赖于轴突和少突胶质前体细胞（OPCs）之间的相互作用。轴突中的动作电位可以随后释放生物活性物质，如谷氨酸，其可以指示OPCs开始髓鞘形成。髓鞘碱性蛋白（MBP）是形成致密髓鞘所需的“髓鞘执行分子”。由于少突胶质细胞谱系（OLC）的细胞能够在纯少突胶质细胞培养物中产生MBP，即没有神经元，我们研究了培养物中发育OLC中的Ca 2+信号传导。我们发现，自发性钙瞬变（CTs）发生在双极OPCs和成熟的少突胶质细胞在非常低的频率。相反，未成熟的OLC（imOLC），具有几个厚突起的细胞，表现出相对高的CT频率。此外，与体细胞CT频率相比，imOLC过程中的CT频率要高得多。体细胞CTs几乎完全被毒胡萝卜素（一种肌质网Ca 2 + ATP酶拮抗剂）和ryanodine（一种ryanodine受体阻断剂）阻断，表明参与了内质网的Ca 2+释放。Ryanodine强烈降低imOLC过程中的CT频率。Na+，K+-ATP酶（NKA）拮抗剂哇巴因（Ouabain）在低浓度时可增加CT频率，而Na+，Ca ~（2+）交换器（NCX）反向阻断剂KB-R7943则可降低CT频率。我们建议，当地RyR-NCX-（NKA？）在没有神经元的情况下，这种相互作用可能是imOLC中CT产生的基础，并且这种活性影响少突胶质细胞的成熟。
Myelination in the central nervous system depends on interactions between axons and oligodendrocyte precursor cells (OPCs). Action potentials in an axon can be followed by release of biologically active substances, like glutamate, which can instruct OPCs to start myelination. Myelin Basic Protein (MBP) is an "executive molecule of myelin" required for the formation of compact myelin. As cells of the oligodendrocyte lineage (OLCs) are capable of producing MBP in pure oligodendrocyte cultures, i.e. without neurons, we investigated Ca2+ signaling in developing OLCs in cultures. We show that spontaneous Ca2+ transients (CTs) occur at very low frequency in both bipolar OPCs and mature oligodendrocytes. In contrast immature OLCs (imOLCs), cells with several thick processes, demonstrate a relatively high frequency of CTs. Moreover, CT frequency in imOLC processes is much higher as compared with the somatic CT frequency. Somatic CTs are almost completely blocked by thapsigargin, an antagonist of sarco-(endo-) plasmic reticulum Ca2+ ATPase, and ryanodine, a blocker of ryanodine receptors, indicating an involvement of Ca2+ release from the endoplasmic reticulum. Ryanodine strongly reduces CT frequency in imOLC processes. Ouabain, an antagonist of Na+, K+-ATPase (NKA), applied at low concentration increases CT frequency, while KB-R7943, a blocker of reverse mode of Na+, Ca2+ exchanger (NCX), decreases CT frequency. We suggest that local RyR-NCX-(NKA?) interaction might underlie the generation of CTs in imOLC in the absence of neurons, and this activity influences oligodendrocyte maturation.