Cannabinoid receptor-mediated inhibition of calcium signaling in rat retinal ganglion cells

Mélanie R. Lalonde, Christine A.B. Jollimore, Kelly Stevens, Steven Barnes, Melanie E.M. Kelly

Résultat de recherche: Articleexamen par les pairs

44 Citations (Scopus)

Résumé

Purpose: The physiological actions of CB1, cannabinoid receptors (CB1Rs) in mammalian retina have yet to be fully described in all cell types. Here we investigate the actions of CB1R activation on high-voltage-activated (HVA) Ca2+ channtel currents in purified cultures of rat retina] ganglion cells (RGCs). Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry were used to determine the presence of CB1R mRNA and protein in a purified RGC culture generated from neonatal rats using a two-step panning procedure. Ruptured-patch whole-cell voltage clamp was used to test the effect of CB1R agonists (WIN 55,212-2) and antagonists (SR 141716A, AM281) on HVA Ca2+ channel currents. Results: RT-PCR analysis contirmed CB1B mKNA in cultured RGCS and immunocytoctiermstry tor CB1R protein revealed labeling in both the cell body and neurites of isolated RGCs. Patch-clamp recording from cultured rat RGCs showed that the CB1R agonist WIN 55,212-2 inhibited HVA Ca2+ channel currents up to 50% in a concentration-dependent manner (0.5, 1, and 5 μM). The Ca2+ channel current inhibition by WIN 55,212-2 was blocked by CB1R antagonists AM281 and SR141716. Conclusions: Activation of CB1Rs in cultured RGCs inhibits HVA Ca2+ channel currents. These data show that cannabinoids can modify the excitability of RGCs and could affect retinal output. This finding has implications for retinal signal processing as'it suggests that endogenous cannabinoids have inhibitory effects on RGCs and that exogenous cannabinoids could modulate retinal function by this pathway as well.

Langue d'origineEnglish
Pages (de-à)1160-1166
Nombre de pages7
JournalMolecular Vision
Volume12
Statut de publicationPublished - oct. 6 2006

ASJC Scopus Subject Areas

  • Ophthalmology

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