Neurotransmitter Coupling through Gap Junctions in the Retina

Neurotransmitter Coupling through Gap Junctions in the Retina
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神经递质通过视网膜间隙连接耦合

DOI:
10.1523/jneurosci.18-24-10594.1998
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发表时间:
1998
期刊:
The Journal of Neuroscience
影响因子:
--
通讯作者:
D. Pow
D. Pow
中科院分区:
--
文献类型:
--
作者:
D. I. Vaney;J. Charles Nelson;D. Pow

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虽然视网膜上所有的双极细胞都可能使用兴奋性递质谷氨酸,但大约一半的锥体双极细胞也含有高水平的抑制性递质甘氨酸。某些类型的锥体双极细胞与杆状无毛细胞形成异种间隙连接,其中含有较高水平的甘氨酸,导致双极细胞从无毛细胞获得甘氨酸的假设。现在,三条独立的证据线为这一假设提供了实验支持。首先,甘氨酸转运蛋白GLYT1在含甘氨酸的无分泌细胞中表达,而在含甘氨酸的双极细胞中不表达,这表明只有无分泌细胞在功能上具有甘氨酸能。其次,间隙连接阻滞剂卡贝诺洛酮大大减少了外源性3h -甘氨酸在双极细胞中的积累,而不是在无腺细胞中的积累。此外,当两类细胞中的内源性甘氨酸储存通过用甘氨酸摄取抑制剂培养视网膜而耗尽时,卡贝诺洛酮阻断双极细胞随后的甘氨酸补充,但不阻断无分泌细胞。第三,细胞内注射带有间隙连接渗透示踪剂的杆状腺增生细胞神经生物素二级标记异质锥体双极细胞群,所有这些细胞都表现出甘氨酸免疫反应性。综上所述,这些发现表明锥体双极细胞中升高的甘氨酸不是通过高亲和力摄取或重新合成产生的,而是通过与甘氨酸能无分泌细胞的间隙连接的神经递质偶联获得的。因此,对于形成异源间隙连接的神经元来说,递质含量可能是一个不可靠的递质功能指标。
Although all bipolar cells in the retina probably use the excitatory transmitter glutamate, approximately half of the cone bipolar cells also contain elevated levels of the inhibitory transmitter glycine. Some types of cone bipolar cells make heterologous gap junctions with rod amacrine cells, which contain elevated levels of glycine, leading to the hypothesis that the bipolar cells obtain their glycine from amacrine cells. Experimental support for this hypothesis is now provided by three independent lines of evidence. First, the glycine transporter GLYT1 is expressed by the glycine-containing amacrine cells but not by the glycine-containing bipolar cells, suggesting that only the amacrine cells are functionally glycinergic. Second, the gap-junction blocker carbenoxolone greatly reduces exogenous 3H-glycine accumulation into the bipolar cells but not the amacrine cells. Moreover, when the endogenous glycine stores in both cell classes are depleted by incubating the retina with a glycine-uptake inhibitor, carbenoxolone blocks the subsequent glycine replenishment of the bipolar cells but not the amacrine cells. Third, intracellular injection of rod amacrine cells with the gap-junction permeant tracer Neurobiotin secondarily labels a heterogenous population of cone bipolar cells, all of which show glycine immunoreactivity. Taken together, these findings indicate that the elevated glycine in cone bipolar cells is not derived by high-affinity uptake or de novo synthesis but is obtained by neurotransmitter coupling through gap junctions with glycinergic amacrine cells. Thus transmitter content may be an unreliable indicator of transmitter function for neurons that make heterologous gap junctions.
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发表时间: 1992-08-01
影响因子: 11.1
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