AMPA KAINATE RECEPTOR ACTIVATION IN MURINE OLIGODENDROCYTE PRECURSOR CELLS LEADS TO ACTIVATION OF A CATION CONDUCTANCE, CALCIUM INFLUX AND BLOCKADE OF DELAYED RECTIFYING K+ CHANNELS
AMPA KAINATE RECEPTOR ACTIVATION IN MURINE OLIGODENDROCYTE PRECURSOR CELLS LEADS TO ACTIVATION OF A CATION CONDUCTANCE, CALCIUM INFLUX AND BLOCKADE OF DELAYED RECTIFYING K+ CHANNELS
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DOI：
10.1016/0306-4522(94)90012-4
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发表时间：
1994-11-01
期刊：
影响因子：
3.3
通讯作者：
KETTENMANN, H
中科院分区：
文献类型：
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作者：
BORGES, K;OHLEMEYER, C;KETTENMANN, H
过去几年的研究表明，神经胶质细胞可以表达大量的神经递质受体。在这项研究中，我们的特点是在少突胶质细胞和他们的前体细胞培养的小鼠大脑中的谷氨酸受体的特性，使用膜片钳技术来测量配体激活电流和fura-2成像系统，以确定游离胞浆Ca 2+浓度（[Ca 2 +]（i））的变化。如前所述，通过其特征形态和其电压门控电流鉴定前体细胞[Sontheimer H.等人（1989）Neuron 2，1135-1145]。配体红藻氨酸盐、domoate和α-氨基-3-羟基-5-甲基异恶唑-4-原（AMPA）以及L-谷氨酸盐（但不是反式-1-氨基-1，3-环戊烷二羧酸盐）在-70 mV的保持电位下引起内向电流，拮抗剂6-氰基-7-硝基喹喔啉-2，3-二酮可逆地阻断谷氨酸盐和红藻氨酸盐诱导的反应，表明AMPA/红藻氨酸盐型谷氨酸盐受体的表达。该响应是由于阳离子电导的激活，如通过分析红藻氨酸盐激活电流的反转电位所揭示的。受体激活伴随着两种额外的反应：（i）[Ca 2 +]增加（i）由去极化和随后的电压门控Ca 2+通道激活介导，（ii）延迟整流K+电流的瞬时阻断，但不包括A型K+电流。K+电流的阻断不是由于[Ca 2 +]（i）的增加，因为当暴露于红藻氨酸盐后未检测到[Ca 2 +]（i）增加时，在无Ca 2+的洗浴液中也观察到K+电流的阻断。与前体细胞相比，少突胶质细胞对谷氨酸或相关配体的反应较弱或根本没有反应，我们得出结论，谷氨酸激活了胶质前体细胞中复杂的生理事件模式，这可能在这些细胞的分化过程中发挥作用。
Studies during the last few years have shown that glial cells can express a large repertoire of neurotransmitter receptors. In this study, we have characterized the properties of a glutamate receptor in oligodendrocytes and their precursor cells from cultures of mouse brain, using the patch-clamp technique to measure ligand-activated currents and a fura-2 imaging system to determine changes in free cytosolic Ca2+ concentration ([Ca2+](i)). The precursor cells were identified by their characteristic morphology and their voltage-gated currents as described previously [Sontheimer H. et al. (1989) Neuron 2, 1135-1145]. The ligands kainate, domoate and ct alpha-amino-3-hydroxy-5-methylisoxazole-4-pro (AMPA), as well as L-glutamate but not trans-1-amino-1,3-cyclopentanedicarboxylate elicited inward currents at a holding potential of -70 mV and the antagonist 6-cyano-7-nitroquinoxaline-2,3-dione blacked the glutamate- and kainate-induced response reversibly, indicating the expression of an AMPA/kainate-type glutamate receptor. The response is due to the activation of a cationic conductance as revealed by analysing the reversal potential of the kainate-activated current. Receptor activation is accompanied by two additional responses: (i) an increase in [Ca2+](i) mediated by depolarization and a subsequent activation of voltage-gated Ca2+ channels and (ii) a transient blockade of a delayed rectifying K+ current, but not of the A-type K+ current. The blockade of the K+ current was not due to the increase in [Ca2+](i) since it was also observed in Ca2+-free bathing solution when no increase in [Ca2+](i) was detectable after exposure to kainate. In contrast to precursor cells, oligodendrocytes responded weakly or not at all to glutamate or related ligands.We conclude that glutamate activates a complex pattern of physiological events in the glial precursor cells, which may play a role during the differentiation process of these cells.