Purchase this article with an account.
M.R. Lalonde, M.E. Kelly, S. Barnes; Cannabinoid Inhibition of Na and Ca Channel Currents in Salamander Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5150.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Endogenous cannabinoids as well as their receptors have been identified throughout the central nervous system, including the retina, where they may be involved in retinal processing. CB1 receptors in tiger salamander are mainly located to the inner retina (Straiker et al., 1999). The objective of the study was to investigate the modulation of Na and high voltage-activated (HVA) Ca channel currents by the synthetic cannabinoid agonist WIN55,212-2 in retinal ganglion cells (RGCs). Methods: Whole-cell, voltage-clamp recordings were performed on larval tiger salamander RGCs. Na channel currents were recorded from RGCs in a mini-slice preparation. HVA Ca channel currents from enzymatically isolated FITC-dextran RGCs were recorded using Ba2+ as the charge carrier. Results: Voltage-gated Na channel currents, which were blocked by 0.1µM TTX (n=4), were significantly reduced to 71% ± 20% (mean ± SD) of control by 5µM WIN55,212-2 (n=5). A decrease in INa occurred in eight out of thirteen cells tested in the presence of 1µM WIN55,212 (20% ± 10%), which was inhibited by 0.5µM of the selective cannabinoid CB1 antagonist SR141716 (97% ± 7%; n=4). One millimolar GDP-ßS, added to the pipette solution to test the possible involvement of G-protein coupling, also prevented any decrease in INa following the application of 1µM WIN55,212-2 (94% ± 18%; n=4). Ba2+-mediated currents through HVA Ca channels, blocked by 100µM CdCl2 and enhanced by 1µM BayK8644, were significantly reduced by the application of 0.5µM WIN55,212-2 (35% ± 20%; n=5). Conclusions: Cannabinoids may be involved in visual processing in RGCs by altering integrative functions through Na and Ca channel modulation. These effects appear mediated via a G-protein coupled mechanism. Further investigation is warranted to better define modulatory interactions and channel inhibitory mechanisms.
This PDF is available to Subscribers Only