AMPA Receptor-Mediated Ca2+ Transients in Mouse Olfactory Ensheathing Cells
AMPA Receptor-Mediated Ca2+ Transients in Mouse Olfactory Ensheathing Cells
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DOI：
10.3389/fncel.2019.00451
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发表时间：
2019-10
影响因子：
5.3
通讯作者：
Antonia Beiersdorfer;C. Lohr
中科院分区：
文献类型：
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作者：
Antonia Beiersdorfer;C. Lohr
神经胶质细胞中的Ca 2+信号主要由代谢途径和随后的Ca 2+从内部Ca 2+库释放触发。然而，有即将到来的证据表明，各种离子通道也可能通过Ca 2+内流启动神经胶质细胞中的Ca 2+升高。我们研究了AMPA受体介导的内向电流和Ca 2+瞬变在嗅鞘细胞（OECs），一个专门的神经胶质细胞群体在嗅球（OB），使用全细胞电压钳记录和共聚焦Ca 2+成像。通过免疫组织化学，我们发现免疫反应AMPA受体亚基GluA 1，GluA 2和GluA 4的OECs，表明AMPA受体的存在OECs。红藻氨酸诱导的内向电流完全由AMPA受体介导，因为它们对特异性AMPA受体拮抗剂GYKI 53655敏感。此外，红藻氨酸诱导的内向电流减少的选择性Ca 2+渗透AMPA受体抑制剂，NASPM，表明功能性Ca 2+渗透AMPA受体的存在下，嗅鞘细胞。此外，红藻氨酸的应用引起的Ca 2+瞬变OECs被取消在细胞外Ca 2+的情况下，表明Ca 2+内流通过Ca 2+渗透AMPA受体有助于红藻氨酸诱导的Ca 2+瞬变。然而，红藻氨酸诱导的Ca 2+瞬变在Ca 2+库耗尽时部分减少，从而得出结论，通过AMPA受体通道的Ca 2+内流对于触发OECs中的Ca 2+瞬变是必不可少的，而Ca 2+从内部库的释放部分地有助于红藻氨酸诱发的Ca 2+响应。OSN轴突的内源性谷氨酸释放引发OEC中的Ca 2+瞬变，同样由代谢型受体（谷氨酸能和嘌呤能）和AMPA受体介导，表明AMPA受体介导的Ca 2+信号传导在轴突-OEC通信中的突出作用。
Ca2+ signaling in glial cells is primarily triggered by metabotropic pathways and the subsequent Ca2+ release from internal Ca2+ stores. However, there is upcoming evidence that various ion channels might also initiate Ca2+ rises in glial cells by Ca2+ influx. We investigated AMPA receptor-mediated inward currents and Ca2+ transients in olfactory ensheathing cells (OECs), a specialized glial cell population in the olfactory bulb (OB), using whole-cell voltage-clamp recordings and confocal Ca2+ imaging. By immunohistochemistry we showed immunoreactivity to the AMPA receptor subunits GluA1, GluA2 and GluA4 in OECs, suggesting the presence of AMPA receptors in OECs. Kainate-induced inward currents were mediated exclusively by AMPA receptors, as they were sensitive to the specific AMPA receptor antagonist, GYKI53655. Moreover, kainate-induced inward currents were reduced by the selective Ca2+-permeable AMPA receptor inhibitor, NASPM, suggesting the presence of functional Ca2+-permeable AMPA receptors in OECs. Additionally, kainate application evoked Ca2+ transients in OECs which were abolished in the absence of extracellular Ca2+, indicating that Ca2+ influx via Ca2+-permeable AMPA receptors contribute to kainate-induced Ca2+ transients. However, kainate-induced Ca2+ transients were partly reduced upon Ca2+ store depletion, leading to the conclusion that Ca2+ influx via AMPA receptor channels is essential to trigger Ca2+ transients in OECs, whereas Ca2+ release from internal stores contributes in part to the kainate-evoked Ca2+ response. Endogenous glutamate release by OSN axons initiated Ca2+ transients in OECs, equally mediated by metabotropic receptors (glutamatergic and purinergic) and AMPA receptors, suggesting a prominent role for AMPA receptor mediated Ca2+ signaling in axon-OEC communication.