Activation of group I metabotropic glutamate receptors regulates the excitability of rat retinal ganglion cells by suppressing Kir and Ih
作者单位：Institutes of Brain Science and Eye ＆ ENT Hospital State Key Laboratory of Medical Neurobiology Shanghai Key Laboratory of Visual Impairment and RestorationCollaborative Innovation Center for Brain Science Fudan University
会议名称：《中国神经科学学会第十二届全国学术会议》
会议日期：2017年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词：mGluR I excitability spontaneous firing Kir Ih retinal ganglion cell
摘 要：Group I metabotropic glutamate receptor（m Glu R 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 m Glu R1 and m Glu R5 antagonists respectively, significantly reduced the firing frequency, suggesting that glutamate endogenously released from bipolar cells constantly modulates RGC firing. DHPG（10 μM）, an m Glu R 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 m Glu R1 subtype. Intracellular Ca2+-dependent PI-PLC/PKC and calcium/calmodulindependent protein kinase II（Ca MKII） 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 Ih currents could be recorded in RGCs, and extracellular application of DHPG indeed suppressed these currents. Our results suggest that activation of m Glu R I regulates the excitability of rat RGCs by inhibiting Kir and Ih.