Linn D M, Massey S C
Sensory Sciences Center, Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston 77030.
Vis Neurosci. 1992 Feb;8(2):97-106. doi: 10.1017/s0952523800009263.
The cholinergic amacrine cells of the rabbit retina may be labeled with [3H]-Ch and the activity of the cholinergic population monitored by following the release of [3H]-ACh. We have tested the effect of muscimol, a potent GABAA agonist, on (1) the light-evoked release of ACh, presumably mediated via bipolar cells, which are known to have a direct input to the cholinergic amacrine cells and (2) ACh release produced by exogenous glutamate analogs that probably have a direct effect on cholinergic amacrine cells. Muscimol blocked the light-evoked release of ACh with an IC50 of 1.0 microM. In contrast, ACh release produced by nonsaturating doses of kainate or NMDA was not reduced even by 100 microM muscimol. Thus, we have been unable to demonstrate a direct effect of GABA on the cholinergic amacrine cells. GABA antagonists, such as picrotoxin, caused a large increase in the base release and potentiated the light-evoked release of ACh. Both these effects were abolished by DNQX, a kainate antagonist that blocks the input to cholinergic amacine cells from bipolar cells. DNQX blocked the effects of picrotoxin even when controls showed that the mechanism of ACh release was still functional. Together, these results imply that the dominant site for the GABA-mediated inhibition of ACh release is on the bipolar cell input to the cholinergic amacrine cells. This is consistent with previous anatomical and physiological evidence that bipolar cells receive negative feedback from GABA amacrine cells.
家兔视网膜的胆碱能无长突细胞可用[3H]-胆碱进行标记，通过追踪[3H]-乙酰胆碱的释放来监测胆碱能群体的活性。我们测试了强效GABAA激动剂蝇蕈醇对以下两方面的影响：（1）推测由双极细胞介导的光诱发的乙酰胆碱释放，已知双极细胞对胆碱能无长突细胞有直接输入；（2）外源性谷氨酸类似物产生的乙酰胆碱释放，这些类似物可能对胆碱能无长突细胞有直接作用。蝇蕈醇以1.0微摩尔的半数抑制浓度阻断了光诱发的乙酰胆碱释放。相比之下，即使使用100微摩尔的蝇蕈醇，非饱和剂量的 kainate 或 NMDA 产生的乙酰胆碱释放也没有减少。因此，我们未能证明GABA对胆碱能无长突细胞有直接作用。GABA拮抗剂，如印防己毒素，会导致基础释放大幅增加，并增强光诱发的乙酰胆碱释放。这两种作用都被DNQX（一种kainate拮抗剂，可阻断双极细胞对胆碱能无长突细胞的输入）消除。即使对照显示乙酰胆碱释放机制仍有功能，DNQX也能阻断印防己毒素的作用。这些结果共同表明，GABA介导的乙酰胆碱释放抑制的主要部位是双极细胞对胆碱能无长突细胞的输入。这与之前的解剖学和生理学证据一致，即双极细胞接受来自GABA无长突细胞的负反馈。
