title: HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure.
abstract: OBJECTIVE
  Vision originates in rods and cones at the outer retina. Already at these early stages, diverse processing schemes shape and enhance image information to permit perception over a wide range of lighting conditions. In this work, we address the role of hyperpolarization-activated and cyclic nucleotide-gated channels 1 (HCN1) in rod photoreceptors for the enhancement of rod system responsivity under conditions of light exposure.
  
  
  METHODS
  To isolate HCN1 channel actions in rod system responses, we generated double mutant mice by crossbreeding Hcn1-/- mice with Cnga3-/- mice in which cones are non-functional. Retinal function in the resulting Hcn1-/- Cnga3-/- animals was followed by means of electroretinography (ERG) up to the age of four month. Retinal imaging via scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) was also performed to exclude potential morphological alterations.
  
  
  RESULTS
  This study on Hcn1-/- Cnga3-/- mutant mice complements our previous work on HCN1 channel function in the retina. We show here in a functional rod-only setting that rod responses following bright light exposure terminate without the counteraction of HCN channels much later than normal. The resulting sustained signal elevation does saturate the retinal network due to an intensity-dependent reduction in the dynamic range. In addition, the lack of rapid adaptational feedback modulation of rod photoreceptor output via HCN1 in this double mutant limits the ability to follow repetitive (flicker) stimuli, particularly under mesopic conditions.
  
  
  CONCLUSIONS
  This work corroborates the hypothesis that, in the absence of HCN1-mediated feedback, the amplitude of rod signals remains at high levels for a prolonged period of time, leading to saturation of the retinal pathways. Our results demonstrate the importance of HCN1 channels for regular vision.
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University of Tübingen, Schleichstr. 4/3, D-72076, Tübingen, Germany.
authors.forename: Vithiyanjali
authors.initials: V
authors.lastname: Sothilingam
authors.affiliation: Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377, München, Germany.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Michalakis
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University of Tübingen, Schleichstr. 4/3, D-72076, Tübingen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Garcia Garrido
authors.affiliation: Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377, München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Biel
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University of Tübingen, Schleichstr. 4/3, D-72076, Tübingen, Germany.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University of Tübingen, Schleichstr. 4/3, D-72076, Tübingen, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism; D004596:Electroretinography; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D041623:Tomography, Optical Coherence; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: C518237:Cnga3 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels