Activation of dopamine D1 receptors enhances the temporal summation and excitability of rat retinal ganglion cells. (4th July 2017)

• Record Type: Journal Article
• Authors: Cui, Peng; Li, Xue-Yan; Zhao, Yuan; Li, Qian; Gao, Feng; Li, Ling-Zhu; Yin, Ning; Sun, Xing-Huai; Wang, Zhongfeng
• Is Part Of: Neuroscience. Volume 355(2017)
• Page Start: 71
• Page End: 83
• Publication Date: 2017-07-04
• Subjects: AC adenylate cyclase -- ACSF artificial cerebral spinal fluid -- DA dopamine -- EGTA ethylene glycol-bis(β-aminoethyl ether)-N, N, N′, N′-tetraacetic acid -- EPSP excitatory postsynaptic potential -- GCL ganglion cell layer -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- Ih hyperpolarization-activated cation currents -- INL inner nuclear layer -- IPL inner plexiform layer -- Kir inwardly rectifying K+ -- mEPSCs miniature excitatory postsynaptic currents -- OPL outer plexiform layer -- PKC protein kinase C -- PLC phospholipase C -- RGCs retinal ganglion cells -- RM one-way ANOVA repeated-measures one-way ANOVA -- TTX tetrodotoxin; dopamine -- D1 receptors -- retinal ganglion cell -- temporal summation -- excitability -- inward rectifying K+ channel; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.04.046
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: The D1 receptor agonist SKF81297 increases EPSP5/EPSP1 ratio in rat retinal ganglion cells. The SKF81297 effect is mediated by mainly suppressing Kir channels. Involvement of the cAMP/PKA signaling pathway in the SKF81297 effect. SKF81297 increases the spontaneous firing and induces depolarization of retinal ganglion cells. Activation of D1 receptors increases the excitability of rat retinal ganglion cells. Abstract: Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques. Bath application of the selective D1 receptor agonist SKF81297 increased the ratio of excitatory postsynaptic potentials (EPSPs) (EPSP5/EPSP1) within an EPSP train evoked by a train stimulation (five current pulses at 40 Hz), which was blocked by co-application of SCH23390, a specific D1 receptor antagonist. Ba 2+, an inwardly rectifying K + channel (Kir) blocker, significantly suppressed the SKF81297-induced effect, whereas ZD7288, a specific hyperpolarization-activated cation current ( I h ) blocker, showed a moderate inhibitory effect. The cAMP/protein kinase A (PKA) signaling pathway, but not phosphoinositide-specific phospholipase C (PI-PLC), mediated the SKF81297-induced modulation of EPSP temporal summation. Further experiments showed that SKF81297 suppressed Ba 2+ -sensitive Kir currents in RGCs. Additionally, SKF81297 increased the spontaneous firing frequency of RGCs, and caused depolarization of the cells with or without the presence of synaptic receptor blockers. In contrast, SKF81297 did not significantly change the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in RGCs. Our results indicate that D1 receptor activation enhances the temporal summation of RGCs mainly by suppressing Kir currents through the cAMP/PKA signaling pathway, thus increasing the excitability of rat RGCs.