Fig. 3.
Melanopsin phototransduction cascade models in ipRGCs. Light activates melanopsin, initiating a biochemical cascade resulting in the depolarization of ipRGCs. Diverse melanopsin phototransduction cascades exist across ipRGC subtypes. Depicted are the current phototransduction models for three ipRGC subtypes. (A) In M1 ipRGCs, melanopsin signals through Gq to target TRPC channels (Warren et al., 2006; Graham et al., 2008; Xue et al., 2011; Jiang et al., 2018; Sonoda et al., 2018). (B) Similarly to M1 cells, M2 ipRGCs activate Gq to modulate TRPC channels, yet unlike M1 ipRGCs, M2 cells in parallel signal through an unknown G-protein to open HCN channels (Jiang et al., 2018; Perez-Leighton et al., 2011). (C) There are two proposed models for M4 ipRGC phototransduction (Sonoda et al., 2018; Jiang et al., 2018). (i) Sonoda et al. (2018) propose that potassium leak channels are the major phototransduction target in M4 ipRGCs with a minor role played by TRPC channels. (ii) HCN channels are the major phototransduction target in M4 cells (Jiang et al., 2018). HCN channels are primarily opened by hyperpolarization and closed by depolarization; however, in this model, HCN channels are activated by cyclic nucleotides. The structure of a cyclic nucleotide is shown above, in which the R represents the nitrogenous base (adenine or guanine) bonded to the sugar phosphate part. Further inquiry is required to explain the opposing melanopsin phototransduction models in M4 ipRGCs. cNMP, cyclic nucleotide monophosphate; HCN, hyperpolarization-activated cyclic nucleotide-gated; PLC, phospholipase C; TRPC, canonical transient receptor potential.