Comparison of glycine and GABA actions on the zebrafish homomeric glycine receptor
Comparison of glycine and GABA actions on the zebrafish homomeric glycine receptor
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DOI：
10.1111/j.1469-7793.1999.0369t.x
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发表时间：
1999-06-01
影响因子：
5.5
通讯作者：
Bregestovski, P
中科院分区：
文献类型：
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作者：
Fucile, S;de Saint Jan, D;Bregestovski, P
1. 甘氨酸和 GABA 可以从相同的突触前末梢共同释放，在低等脊椎动物中，它们可以激活相同的甘氨酸受体 (GlyR)。因此，我们使用两种表达系统：非洲爪蟾卵母细胞和人 BOSC 23 细胞系，检查了这两种抑制性递质对斑马鱼 α Z1 亚基形成的同聚 GlyR 的影响。 2． α Z1 对这些神经递质的表观亲和力 (EC50) 变化很大。在非洲爪蟾卵母细胞中，甘氨酸的 EC50 范围为 37 至 360 muM（平均 +/- S.D. EC50 116 +/- 75 muM，n = 83），GABA.3 的 EC50 范围为 8 至 120 mM（平均 EC50 40 +/- 30 mM，n = 37）。在 BOSC 细胞中，甘氨酸和 GABA 的 EC50 分别为 9 至 92 muM（平均 EC50 33 +/- 17 muM，n = 19）和 0.7 至 19.1 mM（平均 EC50 4.9 +/- 4.7 mM，n = 29）。4． GABA 作为弱激动剂或完全激动剂激活 α Z1 GlyR：其功效（定义为 I-max、I-GABA/I-max、I-Gly）与 EC50 呈指数关系。 GABA 和甘氨酸的 EC50 值之间观察到线性关系。5．在outside-out贴片中，GABA和甘氨酸以相同的单通道电导（85-100 pS）激活α Z1，但动力学不同，并且浓度对甘氨酸的爆发持续时间有显着影响。6．在outside-out贴片中，甘氨酸的失活时间常数与浓度相关，但GABA.7则不然。我们的数据表明，甘氨酸和 G-ABA 与 α Z1 相互作用的动力学是不同的，并且它们决定了这些神经递质对 GlyR 的作用的特性。
1. Glycine and GABA can be co-released from the same presynaptic terminals and in lower vertebrates they can activate the same glycine receptors (GlyRs). Thus we examined the effects of these two inhibitory transmitters on the homomeric GlyRs formed by the alpha Z1 subunit, of the zebrafish using two expression systems: Xenopus oocytes and the human BOSC 23 cell line.2. The apparent affinity (EC50) of alpha Z1 for these neurotransmitters was highly variable. In Xenopus oocytes the EC50 ranged from 37 to 360 mu M (mean +/- S.D. EC50 116 +/- 75 mu M, n = 83) for glycine and from 8 to 120 mM (mean EC50 40 +/- 30 mM, n = 37) for GABA.3. In BOSC cells the EC50 varied from 9 to 92 mu M (mean EC50 33 +/- 17 mu M, n = 19) and from 0.7 to 19.1 mM (mean EC50 4.9 +/- 4.7 mM, n = 29) for glycine and GABA, respectively.4. GABA activated alpha Z1 GlyRs either as a weak or full agonist: its efficacy (defined as I-max,I-GABA/I-max,I-Gly) was related to EC50 by an exponential relationship. A linear relationship was observed between EC50 values for GABA and glycine.5. In outside-out patches, GABA and glycine activated alpha Z1 with identical single-channel conductances (85-100 pS), but with different kinetics and marked effect of concentration on burst duration for glycine only.6. In outside-out patches deactivation time constants were concentration dependent for glycine, but not for GABA.7. Our data demonstrate that the kinetics of glycine and G-ABA interactions with alpha Z1 are different and that they determine the properties of these neurotransmitter actions on the GlyR.