Charpak S, Gähwiler B H, Do K Q, Knöpfel T
Brain Research Institute, University of Zürich, Switzerland.
Nature. 1990 Oct 25;347(6295):765-7. doi: 10.1038/347765a0.
Excitatory amino acids mediate fast synaptic transmission in the central nervous system through the activation of at least three distinct ionotropic receptors: N-methyl-D-aspartate (NMDA), the alpha-amino-3-hydroxy-5-methyl-isoxasole-4-propionate (AMPA)/quisqualate (QUIS) and the kainate subtypes (for reviews, see refs 1, 2). They also activate the additional QUIS 'metabotropic' receptor (sensitive to trans-1-amino-cyclopentyl-1,3-dicarboxylate, ACPD) linked to inositol phospholipid metabolism. We have used hippocampal slice cultures to study the electrophysiological consequences of the metabotropic response. We find that activation of an ACPD-sensitive QUIS receptor produces a 'slow' excitation of CA3 pyramidal cells, resulting from depression of a Ca2(+)-dependent K+ current and a voltage-gated K+ current. Combined voltage-clamp and microfluorometric recordings show that, although these receptors can trigger an increase in intracellular Ca2+ concentration, suppression of K+ currents is independent of changes in intracellular Ca2+. These effects closely resemble those induced by activating muscarinic acetylcholine receptors in the same neurons and suggest that excitatory amino acids not only act as fast ionotropic transmitters but also as slow neuromodulatory transmitters.
N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）/quisqualate（QUIS）和海人藻酸亚型（有关综述，请参见参考文献1、2）。它们还激活与肌醇磷脂代谢相关的额外的QUIS“代谢型”受体（对反式-1-氨基环戊基-1,3-二羧酸，ACPD敏感）。我们利用海马脑片培养物来研究代谢型反应的电生理后果。我们发现，激活对ACPD敏感的QUIS受体可产生CA3锥体细胞的“缓慢”兴奋，这是由Ca2(+)依赖性K+电流和电压门控K+电流的抑制所致。联合电压钳和微量荧光测定记录表明，尽管这些受体可触发细胞内Ca2+浓度升高，但K+电流的抑制与细胞内Ca2+的变化无关。这些效应与在相同神经元中激活毒蕈碱型乙酰胆碱受体所诱导的效应非常相似，表明兴奋性氨基酸不仅作为快速离子型递质起作用，而且还作为缓慢的神经调节递质起作用。
