Somatostatin receptor-mediated suppression of gabaergic synaptic transmission in cultured rat retinal amacrine cells.
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.
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
W
W
Chen
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
J B
JB
Ke
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
H J
HJ
Wu
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Y
Y
Miao
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
F
F
Li
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
X L
XL
Yang
Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. Electronic address: zfwang@fudan.edu.cn.
Z
Z
Wang
D000262:Adenylyl Cyclases / Q000378:metabolism; D025042:Amacrine Cells / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017481:Receptors, Somatostatin; C115977:Sstr2 protein, rat; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; C094573:somatostatin receptor 5; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000262:Adenylyl Cyclases
cAMP–PKA signaling pathway; calcium channels; patch-clamp; spontaneous inhibitory postsynaptic currents