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S.M. Carlson, M. Takao, I. Sherer, F. Dunn, D. Berson; Phototransduction Cascade in Instrinsically Photosensitive Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5184.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A rare ganglion cell type is directly sensitive to light. These intrinsically photosensitive ganglion cells (ipRGCs) contain the presumptive photopigment melanopsin and innervate the suprachiasmatic nucleus (SCN). We sought to identify elements of the phototransduction cascade in ipRGCs. Method: In isolated rat retinas, we made whole cell current- and voltage-clamp recordings from ipRGCs retrolabeled from the SCN. Cyclic GMP was detected immunohistochemically with an antibody kindly donated by Dr. J. de Vente (J Chem Neuroanat 10, 241,'96). Results: Invertebrate phototransduction cascades involve G-proteins of the Gq/11 family, phospholipase C (PLC), diacylglycerol and/or inositol triphosphate, and increases in intracellular free calcium ([Ca2+]i). Transduction in ipRGCs probably does not rely on this signaling pathway. Light responses persisted during blockade either of Gq/11 (GPant-2A; 30 µM internal) or of PLC (bath applied U73122 [10 µM] or neomycin [50 µM]). Photic responses also persisted when [Ca2+]i was chelated (10 mM BAPTA internal or 50 µM BAPTA-AM in the bath), when Co2+ replaced Ca2+ in the bath, and when intracellular Ca2+stores were depleted (10 µM thapsigargin, bath-applied). Thapsigargin did greatly slow post-stimulus response decay. In vertebrate rods and cones, the transduction cascade involves cGMP acting at cyclic nucleotide gated (CNG) channels. We obtained conflicting evidence regarding the presence of such a cascade in ipRGCs. Two bath-applied, membrane-permeant cGMP analogs (Rp- and Sp-8-pCPT-cGMPs; 10 µM and 5 µM, respectively) depolarized ipRGCs and partly occluded their light-evoked currents. (This depolarization is not mediated by protein kinase G because the two analogs used have opposite effects on the enzyme.) However, internal application of the CNG channel blocker, l-cis-diltiazem (200 µM), did not eliminate the light response. Further, ipRGCs did not exhibit a light-evoked, immunohistochemically detectable increase in cGMP. The ipRGCs might possess CNG channels that are not coupled to the phototransduction cascade. Conclusion: These data suggest that ipRGCs may use a phototransduction signaling pathway distinct from both the cyclic nucleotide cascade of vertebrate rods and cones and the phosphoinositide signaling pathway of invertebrate photoreceptors.
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