Eye Institute, Eye & ENT Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Key Laboratory of Myopia (Ministry of Health), Fudan University, Shanghai, 200031, China.
Department of Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Neurosci Lett. 2019 Aug 24;708:134337. doi: 10.1016/j.neulet.2019.134337. Epub 2019 Jun 18.
Somatostatin has been shown to modulate a variety of neuronal functions by activating the five specific G-protein coupled receptors (sst-sst). Here, effects of sst receptor activation on T-type Ca channels in acutely isolated retinal ganglion cells (RGCs) of rats were investigated using whole-cell patch-clamp techniques. The sst receptor specific agonist L-817,818 significantly and reversibly suppressed T-type Ca currents, and shifted inactivation curve of the channels toward hyperpolarization direction. The effect of L-817,818 was in a dose-dependent manner, with an IC being 8.8 μM. Pertussis toxin-sensitive G protein mediated intracellular nitric oxide (NO)/cGMP/protein kinase G (PKG) signaling cascade was involved in the L-817,818 effect on Ca currents because pharmacological interference of each of these signaling molecules abolished the L-817,818 effect. In contrast, neither phospholipase C/protein kinase C nor cAMP/protein kinase A signal pathways seemed likely to be involved because the L-817,818 effect persisted when these signaling pathways were blocked by U73122, bisindolylmaleimide IV, chelerythrine chloride, and Rp-cAMP, respectively. These results suggest that activation of sst receptors suppresses T-type Ca currents in rat RGCs through intracellular NO/cGMP/PKG signaling pathway, which may provide a potential mechanism for protecting RGCs against injury.
生长抑素通过激活五个特定的 G 蛋白偶联受体（sst-sst）来调节多种神经元功能。在这里，使用全细胞膜片钳技术研究了 sst 受体激活对急性分离的大鼠视网膜神经节细胞（RGC）中的 T 型钙通道的影响。sst 受体特异性激动剂 L-817,818 可显著和可逆地抑制 T 型钙电流，并使通道失活曲线向超极化方向移动。L-817,818 的作用呈剂量依赖性，IC 为 8.8 μM。百日咳毒素敏感的 G 蛋白介导的细胞内一氧化氮（NO）/环鸟苷酸（cGMP）/蛋白激酶 G（PKG）信号级联参与了 L-817,818 对钙电流的作用，因为这些信号分子的药理学干扰消除了 L-817,818 的作用。相反，磷脂酶 C/蛋白激酶 C 或 cAMP/蛋白激酶 A 信号通路似乎不太可能参与，因为当这些信号通路分别被 U73122、双吲哚马来酰亚胺 IV、氯化白屈菜红碱和 Rp-cAMP 阻断时，L-817,818 的作用仍然存在。这些结果表明，sst 受体的激活通过细胞内 NO/cGMP/PKG 信号通路抑制大鼠 RGC 中的 T 型钙电流，这可能为保护 RGC 免受损伤提供了一种潜在的机制。
