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Suppression of outward K⁺ currents by WIN55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors.
Neuroscience. 2013 Dec 03; 253:183-93.N

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 WIN55212-2 (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. While 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 the cannabinoid receptor anandamide, 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.

Authors+Show Affiliations

Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24013008

Citation

Zhang, C-Q, et al. "Suppression of Outward K⁺ Currents By WIN55212-2 in Rat Retinal Ganglion Cells Is Independent of CB1/CB2 Receptors." Neuroscience, vol. 253, 2013, pp. 183-93.
Zhang CQ, Wu HJ, Wang SY, et al. Suppression of outward K⁺ currents by WIN55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors. Neuroscience. 2013;253:183-93.
Zhang, C. Q., Wu, H. J., Wang, S. Y., Yin, S., Lu, X. J., Miao, Y., Wang, X. H., Yang, X. L., & Wang, Z. (2013). Suppression of outward K⁺ currents by WIN55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors. Neuroscience, 253, 183-93. https://doi.org/10.1016/j.neuroscience.2013.08.056
Zhang CQ, et al. Suppression of Outward K⁺ Currents By WIN55212-2 in Rat Retinal Ganglion Cells Is Independent of CB1/CB2 Receptors. Neuroscience. 2013 Dec 3;253:183-93. PubMed PMID: 24013008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of outward K⁺ currents by WIN55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors. AU - Zhang,C-Q, AU - Wu,H-J, AU - Wang,S-Y, AU - Yin,S, AU - Lu,X-J, AU - Miao,Y, AU - Wang,X-H, AU - Yang,X-L, AU - Wang,Z, Y1 - 2013/09/05/ PY - 2013/03/16/received PY - 2013/08/25/revised PY - 2013/08/26/accepted PY - 2013/9/10/entrez PY - 2013/9/10/pubmed PY - 2014/6/20/medline KW - 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene KW - 2-AG KW - 2-Arachidonoylglycerol KW - 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid KW - 4-AP KW - 4-aminopyridine KW - AC KW - ACEA KW - AEA KW - BC KW - CB1 receptor KW - CB1/CB2 receptor agonist KW - CB1R KW - CB2 receptor KW - CB2R KW - CB65 KW - DMSO KW - EGTA KW - ERK KW - FAAH KW - Gb KW - HEPES KW - MAPK KW - N-(2-Chloroethyl)-5Z, 8Z,11Z,14Z-eic osatetraenamide KW - N-Cyclohexyl-7-chloro-1-[2-(4-morpholinyl) ethyl]quinolin-4(1H)-one-3-carboxamide KW - PKA KW - RITC KW - TEA KW - TEA-sensitive K(+) current KW - U0126 KW - WIN KW - WIN55212-2 KW - adenylate cyclase KW - anandamide KW - bipolar cell KW - cannabinoid receptor KW - dimethyl sulfoxide KW - eCB KW - endocannabinoid KW - ethylene glycol-bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid KW - extracellular signal-regulated kinase KW - fatty acid amide hydrolase KW - glybenclamide KW - mitogen-activated protein kinase KW - patch-clamp KW - protein kinase A KW - rhodamine-B-isothiocyanate KW - tetraethylammonium KW - Δ(9)-THC KW - Δ(9)-tetrahydrocannabinol SP - 183 EP - 93 JF - Neuroscience JO - Neuroscience VL - 253 N2 - 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 WIN55212-2 (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. While 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 the cannabinoid receptor anandamide, 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24013008/Suppression_of_outward_K⁺_currents_by_WIN55212_2_in_rat_retinal_ganglion_cells_is_independent_of_CB1/CB2_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00752-5 DB - PRIME DP - Unbound Medicine ER -