Li Geng-Lin, Yang Xiong-Li
Institute of Neurobiology, Fudan University, 220 Handan Road, Shanghai 200433, PR China.
Brain Res. 2003 Nov 21;991(1-2):171-9. doi: 10.1016/j.brainres.2003.08.037.
Current responses of carp retinal ganglion cells (RGCs) retrogradely labeled and freshly dissociated to rapid application of glycine were recorded by whole-cell patch clamp techniques and effects of glycine antagonists on these responses were analyzed. The current response to maintained application of glycine at a concentration higher than 30 microM exhibited desensitization, which was well fitted to a monoexponential function. Strychnine (1 microM), a glycine receptor antagonist, completely blocked the response to 100 microM glycine. Strychnine at a concentration range between 10 and 200 nM suppressed the response to 100 microM glycine in a dose-dependent manner, and only a slow-activated and sustained current eventually remained in the presence of 200 nM strychnine. Power spectral density (PSD) analysis revealed no changes in the density-frequency dependence caused by strychnine. It was further shown that dissociation of strychnine from glycine receptors was rather slow. Moreover, Zn(2+) exerted similar dual action on this sustained response and the response in Ringer's: potentiating and reducing them at low and high concentrations of Zn(2+), respectively. 5,7-Dichlorokynurenic acid (DCKA, 500 microM), a selective blocker of the glycine recognition site at the NMDA receptor, partially reduced the glycine response, but without changing its kinetics. These results suggest that glycinergic input to carp ganglion cells may be mediated by strychnine-sensitive glycine receptors with homologous kinetics, and slow dissociation of strychnine from glycine receptors may partially account for the changes in glycine response kinetics occurring in the presence of strychnine.
采用全细胞膜片钳技术记录了经逆行标记并新鲜分离的鲤鱼视网膜神经节细胞(RGCs)对快速施加甘氨酸的电流反应,并分析了甘氨酸拮抗剂对这些反应的影响。对浓度高于30μM的甘氨酸持续施加时的电流反应表现出脱敏现象,该现象很好地符合单指数函数。甘氨酸受体拮抗剂士的宁(1μM)完全阻断了对100μM甘氨酸的反应。浓度在10至200 nM之间的士的宁以剂量依赖性方式抑制了对100μM甘氨酸的反应,在200 nM士的宁存在下最终仅保留缓慢激活的持续电流。功率谱密度(PSD)分析显示士的宁未引起密度-频率依赖性的变化。进一步表明,士的宁从甘氨酸受体上解离相当缓慢。此外,Zn(2+)对这种持续反应和林格氏液中的反应也有类似的双重作用:在低浓度和高浓度的Zn(2+)下分别增强和减弱反应。5,7-二氯犬尿喹啉酸(DCKA,500μM),一种NMDA受体甘氨酸识别位点的选择性阻断剂,部分降低了甘氨酸反应,但未改变其动力学。这些结果表明,鲤鱼神经节细胞的甘氨酸能输入可能由具有同源动力学的士的宁敏感甘氨酸受体介导,士的宁从甘氨酸受体上的缓慢解离可能部分解释了在士的宁存在下甘氨酸反应动力学的变化。