Projects per year
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 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 language | English |
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Article number | e0032-19.2019 |
Number of pages | 13 |
Journal | eNeuro |
Volume | 6 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2019 |
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Dive into the research topics of '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'. Together they form a unique fingerprint.Projects
- 2 Finished
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Understanding cone photoreceptor migration and cell death mechanisms
dos Santos Carvalho, L. (Investigator 01)
ARC Australian Research Council
1/01/14 → 31/12/17
Project: Research
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The Role of Potassium Channels in Photoreceptor Function
Hunt, D. (Investigator 01), Key, B. (Investigator 02), Hart, N. (Investigator 03) & Collin, S. (Investigator 04)
NHMRC National Health and Medical Research Council
1/01/12 → 31/12/14
Project: Research