Regulation of gap junctions by intracellular messengers in retinal neurons

1. 鲤鱼和海龟视网膜中的水平细胞通过间隙连接电耦合，细胞的输入电阻太低而无法测量。然而，将l -精氨酸（一氧化氮（NO）的前体）或花生四烯酸注入水平细胞后，输入电阻显著增加。细胞内注射这些化学物质也阻断了Lucifer Yellow CH在水平细胞中的染料偶联。另一方面，将L-精氨酸与NO合成酶抑制剂N^ g -单甲基-L-精氨酸和N^ g -硝基-L-精氨酸混合注入水平细胞，观察到染料偶联。注射可溶性鸟苷酸环化酶抑制剂，如亚甲基蓝和半胺，也抑制了l -精氨酸的解耦作用。将脂氧合酶抑制剂去二氢愈创木酸（NDGA）与花生四烯酸一起注射到细胞中，观察到染料偶联。注射亚甲基蓝或半胺也抑制花生四烯酸的解耦作用。另一方面，将吲哚美辛（一种环加氧酶抑制剂）与花生四烯酸一起注射到水平细胞中，消除了染料偶联。花生四烯酸与吲哚美辛混合注射后，水平细胞的输入电阻明显增加。这些结果表明，花生四烯酸的一氧化氮（NO）和脂氧合酶代谢产物阻断了视网膜神经元之间的间隙连接，并通过激活鸟苷酸环化酶诱导解耦效应。

1. Horizontal cells in carp and turtle retinas are electrically coupled through gap junctions, and the input resistance of the cells is too low to be measured. However, the input resistance was significantly increased after injection of L-arginine, known as the precursor of nitric oxide (NO), or arachidonic acid into horizontal cells. Intracellular injection of these chemicals also blocked dye-coupling of Lucifer Yellow CH among horizontal cells.2. On the other hand, dye-coupling was observed when the mixture of L- arginine and an NO synthase inhibitor, such as N^G-monomethyl-L-arginine and N^G-nitro-L-arginine, was injected into horizontal cells. Injection of a soluble guanylate cyclase inhibitor, such as methylene blue and cystamine, also suppressed the decoupling effect of L-arginine.3. Dye-coupling was observed when nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was injected into the cells, together with arachidonic acid. Injection of methylene blue or cystamine also suppressed the decoupling effect of arachidonic acid. On the other hand, dye-coupling was eliminated when indomethacin, a cyclo-oxygenase inhibitor, was injected into horizontal cells, together with arachidonic acid. And injection of the mixture of arachidonic acid and indomethacin caused significant increase in the input resistance of horizontal cells.4. These results suggest that nitric oxide (NO) and lipoxygenase metabolites of arachidonic acid block gap junctions between retinal neurons, and that the decoupling effects are induced by activating guanylate cyclase.