Canna~Fangled Abstracts

Suppression of outward K+ currents by win55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors.

By September 10, 2013No Comments
pm2[Epub ahead of print]

Suppression of outward K+ currents by win55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors.

Source

Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.

Abstract

Cannabinoid CB1 receptor (CB1R) signaling system is extensively distributed in the vertebrate retina. Activation of CB1Rs regulates a variety of functions of retinal neurons through modulating different ion channels. In the present work we studied effects of this receptor signaling on K+ channels in retinal ganglion cells by patch-clamp techniques. The CB1R agonist WIN 55212-2 (WIN) suppressed outward K+ currents in acutely isolated rat retinal ganglion cells in a dose-dependent manner, with an IC50 of 4.7 μM. We further showed that WIN mainly suppressed the tetraethylammonium (TEA)-sensitive K+ current component. Whilst CB1Rs were expressed in rat retinal ganglion cells, the WIN effect on K+ currents was not blocked by either AM251/SR141716, specific CB1R antagonists, or AM630, a selective CB2R antagonist. Consistently, cAMP-protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling pathways were unlikely involved in the WIN-induced suppression of the K+ currents because both PKA inhibitors H-89/Rp-cAMP and MAPK/ERK1/2 inhibitor U0126 failed to block the WIN effects. WIN-induced suppression of the K+ currents was not observed when WIN was intracellularly applied. Furthermore, an endogenous ligand of cannabinoid receptor anandamide (AEA), the specific CB1R agonist ACEA and the selective CB2R agonist CB65 also suppressed the K+ currents, and the effects were not blocked by AM251/SR141716 or AM630 respectively. All these results suggest that the WIN-induced suppression of the outward K+ currents in rat retinal ganglion cells, thereby regulating the cell excitability, were not through CB1R/CB2R signaling pathways.
Copyright © 2013. Published by Elsevier Ltd.

KEYWORDS:

1,4-Diamino-2,3-dicyano-1,4-bis [2-a minophenylthio] butadiene’ WIN, WIN 55212-2, 2-AG, 2-Arachidonoylglycerol, 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, 4-AP, 4-aminopyridine, AC, ACEA, AEA, Anandamide, BC, CB1 receptor, CB1/CB2 receptor agonist, CB1R, CB2 receptor, CB2R, CB65, CNS, Cannabinoid receptor, DMSO, EGTA, ERK, FAAH, Gb, HEPES, IPL, MAPK, N-(2-Chloroethyl)-5Z, 8Z,11Z,14Z-eic osatetraenamide, N-Cyclohexyl-7-chloro-1-[2-(4-morpholinyl) ethyl]quinolin-4(1H)-one-3-carboxamide, PKA, PTX, Patch-clamp, RITC, TEA, TEA-sensitive K(+) current, Tetraethylammonium, U0126, adenylate cyclase, anandamide, bipolar cell, central nervous system, dimethyl sulfoxide, eCB, endocannabinoid, ethylene glycol-bis(β-aminoethyl ether) N, N, N’, N’-tetraacetic acid, extracellular signal-regulated kinase, fatty acid amide hydrolase, glybenclamide, inner plexiform layer, mitogen-activated protein kinase, pertussis toxin, protein kinase A, rhodamine-B-isothiocyanate

PMID:

 

24013008

 

[PubMed – as supplied by publisher]
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