McMahon D G, Schmidt K F
Department of Physiology, University of Kentucky, Lexington 40536-0084, USA.
Vis Neurosci. 1999 May-Jun;16(3):425-33. doi: 10.1017/s0952523899163041.
Neurons of the horizontal cell retinal neural network are subject to modulation by the neurotransmitter nitric oxide (NO). We have examined the effects of NO on glutamate receptor function in isolated horizontal cells from the perch (Perca fluviatilis) using the concentration ramp technique to simultaneously record receptor current and agonist concentration. Dose-response curves for glutamate (0-1 mM) and kainate (0-200 microM) were measured in the presence and absence of 1-2 mM sodium nitroprusside (SNP), 1 mM 8-Br-cGMP, 100 microM cyclothiazide or 200 microM dopamine as modulators. SNP increased the EC50 (i.e. decreased affinity) for glutamate and increased Imax (i.e. increased efficacy), whereas 8-Br-cGMP increased EC50, but not Imax. In the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor desensitization blocker cyclothiazide, the SNP-induced increase in EC50 persisted, but the increase in Imax was blocked. The increase in EC50, but not the increase in Imax was also observed when the non-desensitizing agonist kainate (100-200 microM) was applied in the presence of SNP. When 2 mM SNP and 200 microM dopamine were applied together, they increased Imax (740 vs. 2455 pA) and EC50 (422 vs. 682 microM). Our findings indicate that NO modulates horizontal cell glutamate responses by reducing the affinity of receptors for glutamate while simultaneously increasing the maximal current. The shift in affinity is cGMP-mediated and independent of desensitization. The action of NO on horizontal cell glutamate receptors is distinct from, but synergistic with. that of dopamine. Glutamate receptor modulation by NO qualitatively predicts the action of NO on horizontal cell light responses in situ and may alter transmission at visual synapses according to adaptational conditions.
水平细胞视网膜神经网络的神经元受到神经递质一氧化氮（NO）的调节。我们使用浓度斜坡技术，在分离的河鲈（Perca fluviatilis）水平细胞中检测了NO对谷氨酸受体功能的影响，以同时记录受体电流和激动剂浓度。在存在和不存在1-2 mM硝普钠（SNP）、1 mM 8-溴-cGMP、100 microM环噻嗪或200 microM多巴胺作为调节剂的情况下，测量了谷氨酸（0-1 mM）和海人酸（0-200 microM）的剂量反应曲线。SNP增加了谷氨酸的半数有效浓度（EC50，即降低了亲和力）并增加了最大电流（Imax，即增加了效能），而8-溴-cGMP增加了EC50，但未增加Imax。在存在α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体脱敏阻滞剂环噻嗪的情况下，SNP诱导的EC50增加持续存在，但Imax的增加被阻断。当在SNP存在下应用非脱敏激动剂海人酸（100-200 microM）时，也观察到EC50增加，但未观察到Imax增加。当同时应用2 mM SNP和200 microM多巴胺时，它们增加了Imax（740对2455 pA）和EC50（422对682 microM）。我们的研究结果表明，NO通过降低受体对谷氨酸的亲和力同时增加最大电流来调节水平细胞谷氨酸反应。亲和力的变化是由cGMP介导的，且与脱敏无关。NO对水平细胞谷氨酸受体的作用与多巴胺不同，但具有协同作用。NO对谷氨酸受体的调节在质量上预测了NO对原位水平细胞光反应的作用，并可能根据适应条件改变视觉突触处的传递。
