Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells

Zheng Jiang, Wendy W.S. Yue, Lujing Chen, Yanghui Sheng, King Wai Yau

Research output: Contribution to journalArticlepeer-review

Abstract

Non-image-forming vision in mammals is mediated primarily by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, by far the best-studied subtype, melanopsin activates PLCβ4 (phospholipase C-β4) to open TRPC6,7 channels, mechanistically similar to phototransduction in fly rhabdomeric (microvillous) photoreceptors. We report here that, surprisingly, mouse M4-ipRGCs rely on a different and hitherto undescribed melanopsin-driven, ciliary phototransduction mechanism involving cyclic nucleotide as the second messenger and HCN channels rather than CNG channels as the ion channel for phototransduction. Even more surprisingly, within an individual mouse M2-ipRGC, this HCN-channel-dependent, ciliary phototransduction pathway operates in parallel with the TRPC6,7-dependent rhabdomeric pathway. These findings reveal a complex heterogeneity in phototransduction among ipRGCs and, more importantly, break a general dogma about segregation of the two phototransduction motifs, likely with strong evolutionary implications. Discovery in retinal ganglion cells of a ciliary phototransduction pathway that uses cyclic nucleotide as the second messenger and HCN as the effector ion channel has evolutionary implications.

Original languageEnglish (US)
Pages (from-to)652-664.e12
JournalCell
Volume175
Issue number3
DOIs
StatePublished - Oct 18 2018

Keywords

  • HCN channel
  • ciliary phototransduction
  • cyclic-nucleotide pathway
  • ipRGCs
  • melanopsin
  • photoreceptors
  • phototransduction
  • retinal ganglion cells
  • rhabdomeric phototransduction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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