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Dopamine D2 Receptor-Mediated Modulation of Rat Retinal Ganglion Cell Excitability

  • Ning Yin
  • Yu-Long Yang
  • Shuo Cheng
  • Hong-Ning Wang
  • Xin Hu
  • Yanying Miao
  • Fang Li
  • Zhongfeng WangEmail author
Original Article

Abstract

Ganglion cells (RGCs) are the sole output neurons of the retinal circuity. Here, we investigated whether and how dopamine D2 receptors modulate the excitability of dissociated rat RGCs. Application of the selective D2 receptor agonist quinpirole inhibited outward K+ currents, which were mainly mediated by glybenclamide- and 4-aminopyridine-sensitive channels, but not the tetraethylammonium-sensitive channel. In addition, quinpirole selectively enhanced Nav1.6 voltage-gated Na+ currents. The intracellular cAMP/protein kinase A, Ca2+/calmodulin-dependent protein kinase II, and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathways were responsible for the effects of quinpirole on K+ and Na+ currents, while phospholipase C/protein kinase C signaling was not involved. Under current-clamp conditions, the number of action potentials evoked by positive current injection was increased by quinpirole. Our results suggest that D2 receptor activation increases RGC excitability by suppressing outward K+ currents and enhancing Nav1.6 currents, which may affect retinal visual information processing.

Keywords

Retinal ganglion cell Dopamine D2 receptor Outward K+ current Nav1.6 voltage-gated Na+ current Excitability 

Notes

Acknowledgements

We thank Dr. Xiong-Li Yang for helpful discussion and critical comments on the manuscript. This work was supported by grants from the National Natural Science Foundation of China (31671078, 81790642, and 31872765), the Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZJ Lab.

Conflict of interest

The authors declare no potential conflict of interest.

Supplementary material

12264_2019_431_MOESM1_ESM.pdf (377 kb)
Supplementary material 1 (PDF 376 kb)

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  1. 1.Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Zhongshan HospitalFudan UniversityShanghaiChina

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