The role of the voltage-gated potassium channel proteins Kv8.2 and Kv2.1 in vision and retinal disease

insights from the study of mouse gene knock-out mutations

Nathan S. Hart, Jessica K. Mountford, Valentina Voigt, Paula Fuller-Carter, Melanie Barth, Jeanne M. Nerbonne, David M. Hunt, Livia S. Carvalho*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)
15 Downloads (Pure)


Mutations in the KCNV2 gene, which encodes the voltage-gated K + channel protein Kv8.2, cause a distinctive form of cone dystrophy with a supernormal rod response (CDSRR). Kv8.2 channel subunits only form functional channels when combined in a heterotetramer with Kv2.1 subunits encoded by the KCNB1 gene. The CDSRR disease phenotype indicates that photoreceptor adaptation is disrupted. The electroretinogram (ERG) response of affected individuals shows depressed rod and cone activity, but what distinguishes this disease is the supernormal rod response to a bright flash of light. Here, we have utilized knock-out mutations of both genes in the mouse to study the pathophysiology of CDSRR. The Kv8.2 knock-out (KO) mice show many similarities to the human disorder, including a depressed a-wave and an elevated b-wave response with bright light stimulation. Optical coherence tomography (OCT) imaging and immunohistochemistry indicate that the changes in six-month-old Kv8.2 KO retinae are largely limited to the outer nuclear layer (ONL), while outer segments appear intact. In addition, there is a significant increase in TUNEL-positive cells throughout the retina. The Kv2.1 KO and double KO mice also show a severely depressed a-wave, but the elevated b-wave response is absent. Interestingly, in all three KO genotypes, the c-wave is totally absent. The differential response shown here of these KO lines, that either possess homomeric channels or lack channels completely, has provided further insights into the role of K + channels in the generation of the a-, b-, and c-wave components of the ERG.

Original languageEnglish
Article numbere0032-19.2019
Pages (from-to)1-13
Number of pages13
Issue number1
Publication statusPublished - 11 Feb 2019
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • cone dystrophy
  • electroretinogram
  • photoreceptors
  • potassium channels
  • retina
  • retinal degeneration

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