Activation of group I metabotropic glutamate receptors regulates the excitability of rat retinal ganglion cells by suppressing Kir and Ih.
Group I metabotropic glutamate receptor (mGluR I) activation exerts a slow postsynaptic excitatory effect in the CNS. Here, the issues of whether and how this receptor is involved in regulating retinal ganglion cell (RGC) excitability were investigated in retinal slices using patch-clamp techniques. Under physiological conditions, RGCs displayed spontaneous firing. Extracellular application of LY367385 (10 µM)/MPEP (10 µM), selective mGluR1 and mGluR5 antagonists, respectively, significantly reduced the firing frequency, suggesting that glutamate endogenously released from bipolar cells constantly modulates RGC firing. DHPG (10 µM), an mGluR I agonist, significantly increased the firing and caused depolarization of the cells, which were reversed by LY367385, but not by MPEP, suggesting the involvement of the mGluR1 subtype. Intracellular Ca2+-dependent PI-PLC/PKC and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathways mediated the DHPG-induced effects. In the presence of cocktail synaptic blockers (CNQX, D-AP5, bicuculline, and strychnine), which terminated the spontaneous firing in both ON and OFF RGCs, DHPG still induced depolarization and triggered the cells to fire. The DHPG-induced depolarization could not be blocked by TTX. In contrast, Ba2+, an inwardly rectifying potassium channel (Kir) blocker, and Cs+and ZD7288, hyperpolarization-activated cation channel (Ih) blockers, mimicked the effect of DHPG. Furthermore, in the presence of Ba2+/ZD7288, DHPG did not show further effects. Moreover, Kir and Ihcurrents could be recorded in RGCs, and extracellular application of DHPG indeed suppressed these currents. Our results suggest that activation of mGluR I regulates the excitability of rat RGCs by inhibiting Kir and Ih.
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Qian
Q
Li
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Peng
P
Cui
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Yanying
Y
Miao
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Feng
F
Gao
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Xue-Yan
XY
Li
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Wen-Jing
WJ
Qian
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Shu-Xia
SX
Jiang
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.|Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, China.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Na
N
Wu
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China. xhsun@shmu.edu.cn.|Eye & ENT Hospital, Fudan University, Shanghai, 200031, China. xhsun@shmu.edu.cn.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China. xhsun@shmu.edu.cn.|Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, China. xhsun@shmu.edu.cn.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China. xhsun@shmu.edu.cn.
Xing-Huai
XH
Sun
Institutes of Brain Science, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China. zfwang@fudan.edu.cn.|Eye & ENT Hospital, Fudan University, Shanghai, 200031, China. zfwang@fudan.edu.cn.|Institute of Neurobiology, Fudan University, Shanghai, 200032, China. zfwang@fudan.edu.cn.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China. zfwang@fudan.edu.cn.|Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, China. zfwang@fudan.edu.cn.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China. zfwang@fudan.edu.cn.
Zhongfeng
Z
Wang
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000502:physiology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D024661:Potassium Channels, Inwardly Rectifying; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C079694:alpha-methyl-4-carboxyphenylglycine; D008734:Methoxyhydroxyphenylglycol; C121465:6-methyl-2-(phenylethynyl)pyridine; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010738:Type C Phospholipases; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol
Excitability; I h; Kir; Retinal ganglion cell; Spontaneous firing; mGluR I