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

本文讨论了细胞外二价阳离子对递质受体活性的调节作用。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。电流记录从培养的锥体驱动水平细胞或分离的小鼠双极细胞使用全细胞钳模式。在鲶鱼视网膜水平细胞中，当[Ca^<2+>]*浓度增加到10 mM时，IGABA含量增加30%，当[Ca^<2+>]*浓度降低到0.1 mM时，IGABA含量减少65%。在2.5和10 mM [Ca^<2+>]*浓度响应曲线具有相似的Hill系数（1.54和1.24）和EC_<50>值（3.0和3.1 muM）。而10 mM [Ca^<2+>]*的饱和响应幅度大于2.5mM [Ca^<2+>]*的饱和响应幅度。Zn^<2+>对[Ca^<2+>]*增强作用的抑制作用是非竞争性的。当视网膜被照射时，外丛状层的[Ca^<2+>]*增加（-0.5 mM）。在黑暗中，储存在光感受器末端的谷氨酸和Zn^<2+>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，这些变化协同改变GABAc受体的活性，并调节GABAc自身受体介导的正反馈的功效。在小鼠视网膜分离的双极细胞中，检测到GABAA和GABAG受体。在轴突末端发现高密度GABAc受体分布。Zn^<2+>对GABAc受体的抑制作用强于gaba - alpha受体；GABAc的1C_<50>为1.9 muM， GABAA为67.4 muM。如果Zn^<2+>从双极细胞端释放，则会抑制gaba能无分泌细胞向双极细胞端反复的抑制反馈。

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.