Raggenbass M, Pierson P, Metzger D, Alberi S
Department of Physiology, University Medical Centre, Geneva, Switzerland.
Brain Res. 1997 Nov 21;776(1-2):75-87. doi: 10.1016/s0006-8993(97)00945-1.
The mechanism by which (1S,3R)-ACPD, a metabotropic glutamate receptor agonist, induces burst firing in lateral septal neurons of the rat was investigated in coronal brainstem slices. Membrane currents were characterized in voltage clamp using whole-cell recordings. In the presence of (1S,3R)-ACPD, following depolarizing voltage jumps, repolarization towards the holding potential generated an inward aftercurrent. It could have a plateau-like phase and decayed exponentially. This (1S,3R)-ACPD-dependent inward aftercurrent was accompanied by an increase in cell conductance and was reduced following partial replacement of extracellular sodium by N-methyl-D-glucamine. It was unaffected by TEA or barium, and persisted in Cs-loaded neurons or following partial replacement of extracellular chloride by isethionate. This suggests that it was mainly carried by sodium. Loading neurons with the calcium chelator, BAPTA, or blocking transmembrane calcium currents, suppressed the (1S,3R)-ACPD-dependent aftercurrent. By contrast, partial replacement of extracellular sodium by lithium did not affect it. Thus, this current was dependent upon calcium influx but was not due to a sodium/calcium exchanger. It was probably mediated by G protein activation. Indeed, in neurons loaded with GTP-gamma-S, following depolarizing voltage jumps, repolarization towards the holding potential revealed an inward aftercurrent having properties similar to those of the (1S,3R)-ACPD-dependent current. We suggest that (1S,3R)-ACPD induced calcium-activated non-selective channels. In the presence of this agonist, a depolarization-evoked calcium influx could thus evoke a cationic inward current. This current probably promotes the burst firing observed in lateral septal neurons in current clamp.
在冠状脑干切片中研究了代谢型谷氨酸受体激动剂（1S,3R）-ACPD诱导大鼠外侧隔区神经元爆发式放电的机制。使用全细胞记录在电压钳中对膜电流进行了表征。在存在（1S,3R）-ACPD的情况下，去极化电压跃变后，向静息电位的复极化产生内向尾电流。它可能有一个平台样阶段，并呈指数衰减。这种依赖于（1S,3R）-ACPD的内向尾电流伴随着细胞电导的增加，并且在用N-甲基-D-葡糖胺部分替代细胞外钠后减小。它不受TEA或钡的影响，并且在Cs负载的神经元中持续存在，或者在用羟乙基磺酸部分替代细胞外氯后也持续存在。这表明它主要由钠携带。用钙螯合剂BAPTA加载神经元或阻断跨膜钙电流，可抑制依赖于（1S,3R）-ACPD的尾电流。相比之下，用锂部分替代细胞外钠并不影响它。因此，这种电流依赖于钙内流，但不是由于钠/钙交换器。它可能是由G蛋白激活介导的。实际上，在加载了GTP-γ-S的神经元中，去极化电压跃变后，向静息电位的复极化显示出一种内向尾电流，其特性与依赖于（1S,3R）-ACPD的电流相似。我们认为（1S,3R）-ACPD诱导了钙激活的非选择性通道。在这种激动剂存在的情况下，去极化诱发的钙内流因此可以诱发阳离子内向电流。这种电流可能促进了电流钳中在外侧隔区神经元中观察到的爆发式放电。
