Modulation of receptors by the extracellular Ca^<2+> in the retina

视网膜细胞外Ca^<2>对受体的调节

• 批准号: 09680820
• 负责人: KANEDA Makoto
• 金额: $ 2.11万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680820/
• 关键词: horizontal cell; GABA_A; Zn^<2+>; bipolar cell; GABA_C; Ca^<2+>; GABAc受容体

It has been discussed that the activities of transmitter receptors are modulated by extracellular divalent cations. In the present study, we examined the effects of divalent cations (Ca^<2+> and Zn^<2+>) on the GABAc receptor of the catfish retinal horizontal cells and the mouse bipolar cells. Currents were recorded from cultured cone-driven horizontal cells or isolated mouse bipolar cells using a whole cell clamp mode. In catfish retinal horizontal cells, when [Ca^<2+>]* was increased to 10 mM, IGABA was increased by 30 %, while it was reduced to 65 % when [Ca^<2+>]* was lowered to 0.1 mM.The concentration-response curves for IGABA in both 2.5 and 10 mM [Ca^<2+>]* were described with similar Hill coefficients (1.54 and 1.24) and EC_<50> values (3.0 and 3.1 muM). However, the amplitude of the saturation response in 10 mM [Ca^<2+>]* was greater than that in 2.5mM [Ca^<2+>]*. The inhibitory action of Zn^<2+> on the augmenting effect of [Ca^<2+>]* was non-competitive. It has been shown that [Ca^<2+>]* in the outer plexiform layer increases (-0.5 mM) when the retina is illuminated. In the dark, glutamate and Zn^<2+>, stored in photoreceptor terminals, are co-released and accumulate in the synaptic cleft between the photoreceptor and horizontal cells. Thus, these changes cooperatively modify the activity of GABAc receptors, and modulate the efficacy of the positive feedback mediated by GABAc autoreceptor. In isolated bipolar cells of the mouse retina, both GABAA and GABAG receptors were detected. High density GABAc receptor distribution was found at the axon terminal. Zn^<2+> inhibited GABAc receptors more strongly than the GABAALPHA receptors ; 1C_<50> for GABAc was 1.9 muM and that for GABAA was 67.4 muM.If Zn^<2+> is released from the bipolar cell terminal, it would suppress the recurrent inhibitory feedback from GABAergic amacrine cells to the bipolar cell terminal.

已经讨论了递质受体的活性受细胞外二价阳离子的调节。在本研究中，我们研究了二价阳离子（Ca^2+和Zn^2+）对鲶鱼视网膜水平细胞和小鼠双极细胞GABAc受体的影响。使用全细胞钳模式从培养的视锥细胞驱动的水平细胞或分离的小鼠双极细胞记录电流。在鲶鱼视网膜水平细胞中，当[Ca ^2+]* 增加到10 mM时，IGABA增加了30%，而当[Ca ^2 +]* 降低到0.1 mM时，IGABA减少到65%<50>。然而，在10 mM [Ca^2+]* 中的饱和响应幅度大于在2.5 mM [Ca^2+]* 中的饱和响应幅度。Zn^&lt;2+&gt;对[Ca^&lt;2+&gt;]* 增强效应的抑制作用是非竞争性的。已经表明，当视网膜被照射时，外网状层中的[Ca^&lt;2+&gt;]* 增加（~ 0.5 mM）。在黑暗中，储存在光感受器末梢的谷氨酸和Zn^&lt;2+&gt;共同释放并积聚在光感受器和水平细胞之间的突触间隙中。因此，这些变化协同修饰GABAc受体的活性，并调节由GABAc自身受体介导的正反馈的功效。在小鼠视网膜的分离的双极细胞中，检测到GABAA和GABAG受体。轴突终末GABAc受体呈高密度分布。Zn^&lt;2+&gt;对GABAc受体的抑制作用强于GABAALPHA受体，<50>GABAc的IC_1为1.9 μ M，GABAA的IC_1为67.4 μ M。如果Zn^&lt;2+&gt;从双极细胞终末释放，它将抑制GABA能无长突细胞对双极细胞终末的反复抑制性反馈。

项目成果

Kaneda M: "Modulation of GABA_c response by Ca^<2+> and other divalent cations in horizontal cells of the catfish retina." J Gen Physiol. 110. 741-747 (1997)

Kaneda M：“鲶鱼视网膜水平细胞中 Ca^2 和其他二价阳离子对 GABA_c 反应的调节。”