Somatostatin has been shown to modulate a variety of neuronal functions by activating the five specific G-protein coupled receptors (sst(1)-sst(5)). Here, effects of sst(5) receptor activation on T-type Ca2+ channels in acutely isolated retinal ganglion cells (RGCs) of rats were investigated using whole-cell patch-clamp techniques. The sst(5) receptor specific agonist L-817,818 significantly and reversibly suppressed T-type Ca2+ 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 mu M. Pertussis toxin-sensitive G(i/o), protein mediated intracellular nitric oxide (NO)/cGMP/protein kinase G (PKG) signaling cascade was involved in the L-817,818 effect on Ca2+ 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(5) receptors suppresses T-type Ca2+ currents in rat RGCs through intracellular NO/cGMP/PKG signaling pathway, which may provide a potential mechanism for protecting RGCs against injury.
[1]Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Eye & ENT Hosp,Eye Inst, Shanghai 200031, Peoples R China;
[2]Fudan Univ, Minist Hlth, MOE Frontiers Ctr Brain Sci, Key Lab Myopia, Shanghai 200031, Peoples R China;
[3]Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Zhongshan Hosp,Dept Neurol, Shanghai 200032, Peoples R China;
[4]Fudan Univ, Zhongshan Hosp, MOE Frontiers Ctr Brain Sci, Shanghai 200032, Peoples R China
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