Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision

Nat Commun. 2011 Nov 8;2:532. doi: 10.1038/ncomms1540.


Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into ON- and OFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • Cyclic Nucleotide-Gated Cation Channels / metabolism*
  • Electrophysiology
  • Electroretinography
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Retina / metabolism
  • Retina / physiology
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Rod-Cone Interaction / genetics
  • Rod-Cone Interaction / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Vision, Ocular / genetics
  • Vision, Ocular / physiology


  • Cyclic Nucleotide-Gated Cation Channels
  • Hcn1 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Potassium Channels