May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
The Light–Evoked Response of Directly Photosensitive Retinal Ganglion Cells is Blocked by TRPC Channel Inhibitors
Author Affiliations & Notes
  • S. Sekaran
    Visual Neuroscience, Imperial College, London, United Kingdom
  • R.J. Lucas
    Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
  • R.G. Foster
    Visual Neuroscience, Imperial College, London, United Kingdom
  • M.W. Hankins
    Visual Neuroscience, Imperial College, London, United Kingdom
  • Footnotes
    Commercial Relationships  S. Sekaran, None; R.J. Lucas, None; R.G. Foster, None; M.W. Hankins, None.
  • Footnotes
    Support  Wellcome Grant PC2794
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3110. doi:
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      S. Sekaran, R.J. Lucas, R.G. Foster, M.W. Hankins; The Light–Evoked Response of Directly Photosensitive Retinal Ganglion Cells is Blocked by TRPC Channel Inhibitors . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3110.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The light–evoked response in vertebrate rod and cone photoreceptors is associated with the closure of cyclic nucleotide gated (CNG) cation channels. In invertebrate (Drosophila) photoreceptors, the light–evoked response involves the activation of transient receptor potential (TRP) ion channels. Here we investigate the native ion channel that gates the light response in the recently identified directly photosensitive retinal ganglion cells that express the photopigment melanopsin.

Methods: : We employed calcium imaging of the retinal ganglion cell layer in neonatal mice at post–natal days 4–5. Pharmacological blockers of CNG and TRP ion channels were applied by perfusion to isolated retinal preparations.

Results: : Application of 30 µM L–cis diltiazem, a blocker of CNG cation channels, had no significant effect on the light–evoked increase in intracellular Ca2+ (p > 0.05, n = 8 cells). The trivalent ion lanthanum (100 µM), which inhibits voltage gated Ca2+ channel activity and TRP ion channels, induced a partial block of the light response (p < 0.05, n = 9 cells). The TRPC channel blockers 2–aminoethoxydiphenylborane (2–APB; 100 µM; p < 0.01, n = 7 cells) or SKF 96365 (100 µM; p < 0.05, n = 5 cells) completely inhibited the light–evoked response. 2–APB was effective at concentrations as low as 500 nM. Application of 5 µM thapsigargin, a blocker of endoplasmic reticulum Ca2+–ATPases, induced a small by significant increase in the light–evoked response (p < 0.05, n = 5 cells), suggesting that the effects of 2–APB and SKF 96365 were not dependent on store–operated calcium entry.

Conclusions: : The results suggest that in directly photosensitive retinal ganglion cells, activated melanopsin couples to a signalling pathway that ultimately results in the opening of TRPC ion channels.

Keywords: ganglion cells • ion channels • receptors: pharmacology/physiology 
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