Isomura Y, Sugimoto M, Fujiwara-Tsukamoto Y, Yamamoto-Muraki S, Yamada J, Fukuda A
Department of System Neuroscience, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
J Neurophysiol. 2003 Oct;90(4):2752-6. doi: 10.1152/jn.00142.2003.
It is known that GABA, a major inhibitory transmitter in the CNS, acts as an excitatory (or depolarizing) transmitter transiently after intense GABAA receptor activation in adult brains. The depolarizing effect is considered to be dependent on two GABAA receptor-permeable anions, chloride (Cl-) and bicarbonate (HCO3-). However, little is known about their spatial and temporal profiles during the GABAergic depolarization in postsynaptic neurons. In the present study, we show that the amplitude of synaptically induced depolarizing response was correlated with intracellular Cl- accumulation in the soma of mature hippocampal CA1 pyramidal cells, by using whole cell patch-clamp recording and Cl- imaging technique with a Cl- indicator 6-methoxy-N-ethylquinolinium iodide (MEQ). The synaptically activated Cl- accumulation was mediated dominantly through GABAA receptors. Basket cells, a subclass of fast-spiking interneurons innervating the somatic portion of the pyramidal cells, actually fired at high frequency during the Cl- accumulation accompanying the depolarizing responses. These results suggest synaptically activated GABAA-mediated Cl- accumulation may play a critical role in generation of an excitatory GABAergic response in the mature pyramidal cells receiving intense synaptic inputs. This may be the first demonstration of microscopic visualization of intracellular Cl- accumulation during synaptic activation.
已知γ-氨基丁酸（GABA）是中枢神经系统中的主要抑制性神经递质，在成人大脑中，GABAA受体被强烈激活后，它会短暂地作为兴奋性（或去极化）神经递质起作用。这种去极化作用被认为依赖于两种GABAA受体可通透的阴离子，即氯离子（Cl-）和碳酸氢根离子（HCO3-）。然而，关于突触后神经元中GABA能去极化过程中它们的时空分布情况却知之甚少。在本研究中，我们通过全细胞膜片钳记录以及使用氯离子指示剂6-甲氧基-N-乙基喹啉碘化物（MEQ）的氯离子成像技术表明，在成熟海马CA1锥体神经元的胞体中，突触诱导的去极化反应幅度与细胞内氯离子积累相关。突触激活的氯离子积累主要通过GABAA受体介导。篮状细胞是支配锥体神经元胞体部分的快速放电中间神经元的一个亚类，在伴随去极化反应的氯离子积累过程中，它们实际上以高频放电。这些结果表明，突触激活的GABAA介导的氯离子积累可能在接受强烈突触输入的成熟锥体神经元中兴奋性GABA能反应的产生中起关键作用。这可能是首次对突触激活过程中细胞内氯离子积累进行微观可视化的证明。
