Activation of somatostatin receptor 5 suppresses T-type Ca2+ channels through NO/cGMP/PKG signaling pathway in rat retinal ganglion cells. (24th August 2019)

• Record Type: Journal Article
• Authors: Li, Qian; Zhang, Yi; Wu, Na; Yin, Ning; Sun, Xing-Huai; Wang, Zhongfeng
• Is Part Of: Neuroscience letters. Volume 708(2019)
• Publication Date: 2019-08-24
• Subjects: Bis IV bisindolylmaleimide IV -- INL inner nuclear layer -- L-NMMA NG-monomethyl-l-arginine acetate -- PKA protein kinase A -- PKC protein kinase C -- PKG protein kinase G -- PLC phospholipase C -- PTX pertussis toxin -- RGCs retinal ganglion cells -- NO nitric oxide -- NOS nitric oxide synthetase -- TTX tetrodotoxin; sst5 receptors -- T-type Ca2+channels -- NO/cGMP/PKG signal pathway -- Retinal ganglion cells; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2019.134337
• Languages: English
• ISSNs: 0304-3940

Abstract

Graphical abstract: Highlights: Activation of sst5 suppresses T-type Ca 2+ currents in rat RGCs. Activation of sst5 increases the inactivation probability of T-type Ca 2+ channels. The sst5 effect is mediated by NO/cGMP/PKG signaling pathway. PLC/PKC and cAMP/PKA signaling pathways are not involved in the sst5 effects. Abstract: Somatostatin has been shown to modulate a variety of neuronal functions by activating the five specific G-protein coupled receptors (sst1 -sst5 ). Here, effects of sst5 receptor activation on T-type Ca 2+ channels in acutely isolated retinal ganglion cells (RGCs) of rats were investigated using whole-cell patch-clamp techniques. The sst5 receptor specific agonist L-817, 818 significantly and reversibly suppressed T-type Ca 2+ 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 IC50 being 8.8 μM. Pertussis toxin-sensitive Gi/o protein mediated intracellular nitric oxide (NO)/cGMP/protein kinase G (PKG) signaling cascade was involved in the L-817, 818 effect on Ca 2+ 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 sst5 receptors suppresses T-type Ca 2+ currents in rat RGCs through intracellular NO/cGMP/PKG signaling pathway, which may provide a potential mechanism for protecting RGCs against injury.