Borges K, Ohlemeyer C, Trotter J, Kettenmann H
Department of Neurobiology, Im Neuenheimer Feld 345, Heidelberg, Germany.
Neuroscience. 1994 Nov;63(1):135-49. doi: 10.1016/0306-4522(94)90012-4.
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 alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (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 blocked 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 Ca(2+)-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.
过去几年的研究表明，神经胶质细胞能够表达大量种类的神经递质受体。在本研究中，我们利用膜片钳技术测量配体激活电流，并使用fura-2成像系统测定游离胞质Ca2+浓度（[Ca2+]i）的变化，对来自小鼠脑培养物中的少突胶质细胞及其前体细胞中的谷氨酸受体特性进行了表征。如先前所述[Sontheimer H.等人（1989年）《神经元》2，1135 - 1145]，通过其特征形态和电压门控电流来识别前体细胞。在 - 70 mV的钳制电位下，激动剂海人藻酸、软骨藻酸和α - 氨基 - 3 - 羟基 - 5 - 甲基异恶唑 - 4 - 丙酸（AMPA）以及L - 谷氨酸能引发内向电流，但反式 - 1 - 氨基 - 1,3 - 环戊烷二羧酸不能，并且拮抗剂6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮可逆地阻断谷氨酸和海人藻酸诱导的反应，表明表达了AMPA/海人藻酸型谷氨酸受体。通过分析海人藻酸激活电流的反转电位可知，该反应是由于阳离子电导的激活。受体激活还伴随着另外两种反应：（i）由去极化介导的[Ca2+]i增加以及随后电压门控Ca2+通道的激活；（ii）延迟整流K+电流的瞬时阻断，但A - 型K+电流未被阻断。K+电流的阻断不是由于[Ca2+]i的增加，因为在无Ca2+的浴液中，当暴露于海人藻酸后未检测到[Ca2+]i增加时也观察到了这种阻断。与前体细胞不同，少突胶质细胞对谷氨酸或相关配体反应微弱或根本无反应。我们得出结论，谷氨酸在神经胶质前体细胞中激活了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。
