HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure

Sothilingam, Vithiyanjali; Michalakis, Stylianos; Garrido, Marina Garcia; Biel, Martin; Tanimoto, Naoyuki und Seeliger, Mathias W. (2016): HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure.
In: PLOS ONE 11(1), e0147728

Abstract

Purpose 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1932-6203
• Sprache: Englisch