Activation of somatostatin receptor 5 suppresses T-type Ca channels through NO/cGMP/PKG signaling pathway in rat retinal ganglion cells.

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.