Backus K H, Elsen F P, Schulze C H
Abteilung für Allgemeine Zoologie, FB Biologie, Universität Kaiserslautern, Deutschland.
Glia. 1998 May;23(1):35-44.
The effects of kainate on membrane current and membrane conductance were investigated in presumed hilar glial precursor cells of juvenile rats. The perforated-patch configuration was used also to reveal possible second-messenger effects. Kainate evoked an inward current that was accompanied by a biphasic change in membrane conductance in 69% of the cells. An initial conductance increase with a time course similar to that of the inward current was followed by a second delayed conductance increase. This second conductance was absent in whole-cell-clamp recordings, suggesting that it was mediated by a second messenger effect. Analysis of the reversal potentials of the membrane current during both phases of the kainate-induced conductance change revealed that the first conductance increase reflected the activation of AMPA receptors. Several lines of evidence suggest that the delayed second conductance increase was due to the indirect activation of Ca2+-dependent K+ channels via Ca2+-influx through AMPA receptors. (1) the delayed second conductance increase was blocked by Ba2+ and the reversal of its underlying current was significantly shifted towards EK+, suggesting that it is due to the activation of K+ channels. (2) The delayed second conductance increase disappeared in a Ca2+-free saline buffered with BAPTA, indicating that it depended on Ca2+-influx. (3) Co2+, Cd2+ and nimodipine failed to block the delayed second conductance increase excluding a major contribution of voltage-dependent Ca2+ channels. (4) The involvement of metabotropic glutamate receptors also appeared unlikely, because the kainate-induced delayed second conductance increase could not be blocked by a depletion of the intracellular Ca2+ stores with the Ca2+-ATPase inhibitor thapsigargin, and t-ACPD exerted no effect on membrane current and conductance. We conclude that kainate activates directly AMPA receptors in presumed hilar glial precursor cells. This results in a Ca2+ influx that could lead indirectly to the activation of Ca2+-dependent K+ channels.
在幼年大鼠假定的海马门区神经胶质前体细胞中，研究了红藻氨酸对膜电流和膜电导的影响。采用穿孔膜片钳记录模式来揭示可能的第二信使效应。在69%的细胞中，红藻氨酸诱发内向电流，并伴有膜电导的双相变化。最初，电导增加，其时间进程与内向电流相似，随后是第二次延迟的电导增加。在全细胞钳记录中没有出现这种第二次电导增加，这表明它是由第二信使效应介导的。在红藻氨酸诱导的电导变化的两个阶段，对膜电流的反转电位进行分析，结果表明，第一次电导增加反映了AMPA受体的激活。几条证据表明，延迟的第二次电导增加是由于通过AMPA受体的Ca2+内流间接激活了Ca2+依赖性K+通道。（1）延迟的第二次电导增加被Ba2+阻断，其基础电流的反转明显向EK+偏移，这表明它是由K+通道的激活引起的。（2）在含有BAPTA缓冲的无Ca2+盐溶液中，延迟的第二次电导增加消失，这表明它依赖于Ca2+内流。（3）Co2+、Cd2+和尼莫地平未能阻断延迟的第二次电导增加，排除了电压依赖性Ca2+通道的主要作用。（4）代谢型谷氨酸受体的参与似乎也不太可能，因为红藻氨酸诱导的延迟的第二次电导增加不能被Ca2+ - ATP酶抑制剂毒胡萝卜素耗尽细胞内Ca2+储存所阻断，而且反式-ACPD对膜电流和电导没有影响。我们得出结论，红藻氨酸在假定的海马门区神经胶质前体细胞中直接激活AMPA受体。这导致Ca2+内流，进而可能间接导致Ca2+依赖性K+通道的激活。
