Al-Noori S, Swann J W
The Cain Foundation Laboratories, Baylor College of Medicine, Houston, TX 77030, USA.
Neuroscience. 2000;101(2):337-48. doi: 10.1016/s0306-4522(00)00384-5.
Excitotoxic injury of the dendrites of inhibitory interneurons could lead to decreases in their synaptic activation and explain subsequent local circuit hyperexcitability and epilepsy. A hallmark of dendrotoxicity, at least in principal neurons of the hippocampus and cortex, is focal or varicose swellings of dendritic arbors. In experiments reported here, transient (1h) exposure of hippocampal explant cultures to kainic acid produced marked focal swellings of the dendrites of parvalbumin-immunoreactive pyramidal basket cells in a highly reproducible and dose-dependent manner. At 5mM kainic acid, more than half of the immunopositive apical dendrites in area CA(1) had a beaded appearance. However, the somal volumes of these cells were unaltered by the same treatment. The presence of focal swellings was reversible with kainate washout and was not accompanied by interneuronal cell death. In contrast, exposure to much higher concentrations (300mM) of kainic acid resulted in the total loss of parvalbumin-positive interneurons from explants. Surprisingly, kainic acid-induced dendritic beading does not appear to be mediated by extracellular calcium. Beading was unaltered in the presence of N-methyl-D-aspartate receptor antagonists, the L-type calcium channel antagonist, nimodipine, cadmium, or by removing extracellular calcium. However, blockade of voltage-gated sodium channels by either tetrodotoxin or lidocaine abolished dendritic beading, while the activation of existing voltage-gated sodium channels by veratridine mimicked the kainic acid-induced dendritic beading. Finally, the removal of extracellular chloride prevented the kainic acid-induced dendritic beading.Thus, we suggest that the movement of Na(+) and Cl(-), rather than Ca(2+), into cells underlies the focal swellings of interneuron dendrites in hippocampus.
抑制性中间神经元树突的兴奋毒性损伤可能导致其突触激活减少，并解释随后的局部回路过度兴奋和癫痫。至少在海马体和皮质的主要神经元中，树突毒性的一个标志是树突分支的局灶性或曲张性肿胀。在本文报道的实验中，海马体外植体培养物短暂（1小时）暴露于 kainic 酸会以高度可重复且剂量依赖的方式使小白蛋白免疫反应性锥体细胞篮状细胞的树突出现明显的局灶性肿胀。在5mM kainic 酸作用下，CA(1)区超过一半的免疫阳性顶树突呈现串珠状外观。然而，相同处理并未改变这些细胞的胞体体积。局灶性肿胀在洗去 kainate 后是可逆的，并且不伴有中间神经元细胞死亡。相比之下，暴露于更高浓度（300mM）的 kainic 酸会导致外植体中 parvalbumin 阳性中间神经元完全丧失。令人惊讶的是，kainic 酸诱导的树突串珠现象似乎不是由细胞外钙介导的。在存在 N - 甲基 - D - 天冬氨酸受体拮抗剂、L 型钙通道拮抗剂尼莫地平、镉的情况下，或者去除细胞外钙时，串珠现象均未改变。然而，河豚毒素或利多卡因阻断电压门控钠通道可消除树突串珠现象，而藜芦碱激活现有的电压门控钠通道则可模拟 kainic 酸诱导的树突串珠现象。最后，去除细胞外氯离子可防止 kainic 酸诱导的树突串珠现象。因此，我们认为 Na(+)和 Cl(-)而非 Ca(2+)进入细胞是海马体中间神经元树突局灶性肿胀的基础。
