Journal article
Differential impact of Kv8.2 loss on rod and cone signaling and degeneration
Human molecular genetics, Vol.31(7), pp.1035-1050
10/15/2021
DOI: 10.1093/hmg/ddab301
PMCID: PMC8976434
PMID: 34652420
Abstract
Abstract Heteromeric Kv2.1/Kv8.2 channels are voltage-gated potassium channels localized to the photoreceptor inner segment. They carry IKx, which is largely responsible for setting the photoreceptor resting membrane potential. Mutations in Kv8.2 result in childhood-onset Cone Dystrophy with Supernormal Rod Response (CDSRR). We generated a Kv8.2 knockout (KO) mouse and examined retinal signaling and photoreceptor degeneration to gain deeper insight into the complex phenotypes of this disease. Using electroretinograms we show that there were delayed or reduced signaling from rods depending on the intensity of the light stimulus, consistent with reduced capacity for light-evoked changes in membrane potential. The delayed response was not seen ex vivo where extracellular potassium levels were controlled by the perfusion buffer, so we propose the in vivo alteration is influenced by genotype-associated ionic imbalance. We observed mild retinal degeneration. Signaling from cones was reduced but there was no loss of cone density. Loss of Kv8.2 altered responses to flickering light with responses attenuated at high frequencies and altered in shape at low frequencies. The Kv8.2 KO line on an all-cone retina background had reduced cone-driven ERG b wave amplitudes and underwent degeneration. Altogether, we provide insight into how a deficit in the dark current affects the health and function of photoreceptors.
Details
- Title: Subtitle
- Differential impact of Kv8.2 loss on rod and cone signaling and degeneration
- Creators
- Shivangi M Inamdar - University of IowaColten K Lankford - University of IowaDeepak Poria - Washington University in St. LouisJoseph G Laird - University of IowaEduardo Solessio - SUNY Upstate Medical UniversityVladimir J Kefalov - University of California, IrvineSheila A Baker - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.31(7), pp.1035-1050
- DOI
- 10.1093/hmg/ddab301
- PMID
- 34652420
- PMCID
- PMC8976434
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Grant note
- DOI: 10.13039/100000053, name: National Eye Institute, award: R01 EY020542, R01s EY027387, EY030912, R01 EY026216
- Language
- English
- Date published
- 10/15/2021
- Academic Unit
- Iowa Neuroscience Institute; Biochemistry and Molecular Biology; University College Courses; Ophthalmology and Visual Sciences
- Record Identifier
- 9984187040702771
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