Suppression of outward K(+) currents by activating dopamine D1 receptors in rat retinal ganglion cells through PKA and CaMKII signaling pathways

Qian Li; Na Wu; Peng Cui; Feng Gao; Wen-Jing Qian; Yanying Miao; Xing-Huai Sun; Zhongfeng Wang

doi:10.1016/j.brainres.2016.01.039

Suppression of outward K(+) currents by activating dopamine D1 receptors in rat retinal ganglion cells through PKA and CaMKII signaling pathways

Brain Res. 2016 Mar 15:1635:95-104. doi: 10.1016/j.brainres.2016.01.039. Epub 2016 Jan 27.

Authors

Qian Li¹, Na Wu², Peng Cui³, Feng Gao⁴, Wen-Jing Qian⁵, Yanying Miao⁶, Xing-Huai Sun⁷, Zhongfeng Wang⁸

Affiliations

¹ Institutes of Brain Science, Fudan University, 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. Electronic address: 14110700008@fudan.edu.cn.
² Institutes of Brain Science, Fudan University, Shanghai 200032, China; Department of Ophthalmology at 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. Electronic address: tgf_b@sina.cn.
³ Institutes of Brain Science, Fudan University, 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. Electronic address: 14111520017@fudan.edu.cn.
⁴ Institutes of Brain Science, Fudan University, Shanghai 200032, China; Department of Ophthalmology at 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. Electronic address: fenggao@fudan.edu.cn.
⁵ Institutes of Brain Science, Fudan University, 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. Electronic address: 15111520021@fudan.edu.cn.
⁶ Institutes of Brain Science, Fudan University, 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. Electronic address: yymiao@fudan.edu.cn.
⁷ Institutes of Brain Science, Fudan University, Shanghai 200032, China; Department of Ophthalmology at 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. Electronic address: xhsun@shmu.edu.cn.
⁸ Institutes of Brain Science, Fudan University, Shanghai 200032, China; Department of Ophthalmology at Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Institute of Neurobiology, Fudan University, Shanghai 200032, 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. Electronic address: zfwang@fudan.edu.cn.

PMID: 26826585
DOI: 10.1016/j.brainres.2016.01.039

Abstract

Dopamine plays an important role in regulating neuronal functions in the central nervous system by activating the specific G-protein coupled receptors. Both D1 and D2 dopamine receptors are extensively distributed in the retinal neurons. In the present study, we investigated the effects of D1 receptor signaling on outward K(+) currents in acutely isolated rat retinal ganglion cells (RGCs) by patch-clamp techniques. Extracellular application of SKF81297 (10 μM), a specific D1 receptor agonist, significantly and reversibly suppressed outward K(+) currents of the cells, which was reversed by SCH23390 (10 μM), a selective D1 receptor antagonist. We further showed that SKF81297 mainly suppressed the glybenclamide (Gb)- and 4-aminopyridine (4-AP)-sensitive K(+) current components, but did not show effect on the tetraethylammonium (TEA)-sensitive one. Both protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathways were likely involved in the SKF81297-induced suppression of the K(+) currents since either Rp-cAMP (10 μM), a cAMP/PKA signaling inhibitor, or KN-93 (10 μM), a specific CaMKII inhibitor, eliminated the SKF81297 effect. In contrast, neither protein kinase C (PKC) nor mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway seemed likely to be involved because both the PKC inhibitor bisindolylmaleimide IV (Bis IV) (10 μM) and the MAPK/ERK1/2 inhibitor U0126 (10 μM) did not block the SKF81297-induced suppression of the K(+) currents. These results suggest that activation of D1 receptors suppresses the Gb- and 4-AP-sensitive K(+) current components in rat RGCs through the intracellular PKA and CaMKII signaling pathways, thus modulating the RGC excitability.

Keywords: Dopamine D1 receptor; Outward K(+) currents; Patch-clamp; Retinal ganglion cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzazepines / pharmacology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism*
Male
Potassium Channels / physiology*
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 / agonists
Receptors, Dopamine D1 / antagonists & inhibitors
Receptors, Dopamine D1 / physiology*
Retinal Ganglion Cells / drug effects
Retinal Ganglion Cells / metabolism
Retinal Ganglion Cells / physiology*
Signal Transduction

Substances

Benzazepines
Potassium Channels
Receptors, Dopamine D1
SCH 23390
SK&F 81297
Cyclic AMP-Dependent Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinase Type 2