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Neuroscience. 2014 Jul 25;273:118-27. doi: 10.1016/j.neuroscience.2014.05.013. Epub 2014 May 15.

Somatostatin receptor-mediated suppression of gabaergic synaptic transmission in cultured rat retinal amacrine cells.

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  • 1Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
  • 2Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. Electronic address: zfwang@fudan.edu.cn.

Abstract

Somatostatin (SRIF) modulates neurotransmitter release by activating the specific receptors (sst1-sst5). Our previous study showed that sst5 receptors are expressed in rat retinal GABAergic amacrine cells. Here, we investigated modulation of GABA release by SRIF in cultured amacrine cells, using patch-clamp techniques. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in the amacrine cells was significantly reduced by SRIF, which was partially reversed by BIM 23056, an sst5 receptor antagonist, and was further rescued by addition of CYN-154806, an sst2 receptor antagonist. Both nimodipine, an L-type Ca2+ channel blocker, and ω-conotoxin GVIA, an N-type Ca2+ channel blocker, suppressed the sIPSC frequency, and in the presence of nimodipine and ω-conotoxin GVIA, SRIF failed to further suppress the sIPSC frequency. Extracellular application of forskolin, an activator of adenylate cyclase, increased the sIPSC frequency, while the membrane permeable protein kinase A (PKA) inhibitor Rp-cAMP reduced it, and in the presence of Rp-cAMP, SRIF did not change sIPSCs. However, SRIF persisted to suppress the sIPSCs in the presence of KT5823, a protein kinase G (PKG) inhibitor. Moreover, pre-incubation with Bis IV, a protein kinase C (PKC) inhibitor, or pre-application of xestospongin C, an inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor, SRIF still suppressed the sIPSC frequency. All these results suggest that SRIF suppresses GABA release from the amacrine cells by inhibiting presynaptic Ca2+ channels, in part through activating sst5/sst2 receptors, a process that is mediated by the intracellular cAMP-PKA signaling pathway.

Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

cAMP–PKA signaling pathway; calcium channels; patch-clamp; spontaneous inhibitory postsynaptic currents

PMID:
24846611
[PubMed - in process]
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