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

ENeuro
Nathan S HartLivia S Carvalho

Abstract

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 th...Continue Reading

Citations

May 23, 2020·Ophthalmic Genetics·Thales A C De GuimaraesMichel Michaelides
Sep 25, 2020·International Journal of Molecular Sciences·Meha Kabra, Bikash Ranjan Pattnaik
Mar 31, 2019·Documenta Ophthalmologica. Advances in Ophthalmology·Frederick T CollisonJ Jason McAnany
Dec 1, 2020·Frontiers in Cellular Neuroscience·Colten K LankfordSheila A Baker
Dec 15, 2020·American Journal of Ophthalmology·Michalis GeorgiouMichel Michaelides
Jul 14, 2021·Pflügers Archiv : European journal of physiology·Rabab RashwanLivia S Carvalho
Oct 16, 2021·Human Molecular Genetics·Shivangi M InamdarSheila A Baker

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Methods Mentioned

BETA
gene knock-out
PCR
light microscopy

Software Mentioned

GraphPad
FiJi ImageJ
CDSRR

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