Version 1
: Received: 10 May 2023 / Approved: 11 May 2023 / Online: 11 May 2023 (11:34:36 CEST)
How to cite:
Kleinlogel, S.; Schilardi, G.; Kralik, J. Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling. Preprints2023, 2023050848. https://doi.org/10.20944/preprints202305.0848.v1
Kleinlogel, S.; Schilardi, G.; Kralik, J. Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling. Preprints 2023, 2023050848. https://doi.org/10.20944/preprints202305.0848.v1
Kleinlogel, S.; Schilardi, G.; Kralik, J. Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling. Preprints2023, 2023050848. https://doi.org/10.20944/preprints202305.0848.v1
APA Style
Kleinlogel, S., Schilardi, G., & Kralik, J. (2023). Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling. Preprints. https://doi.org/10.20944/preprints202305.0848.v1
Chicago/Turabian Style
Kleinlogel, S., Giulia Schilardi and Jakub Kralik. 2023 "Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling" Preprints. https://doi.org/10.20944/preprints202305.0848.v1
Abstract
Loss of photoreceptors in retinal degenerative diseases also impacts the inner retina: bipolar cell dendrites retract, neurons rewire and protein expression changes. ON-bipolar cells represent an attractive target for optogenetic vision restoration. However, above-described maladaptations may negatively impact the quality of restored vision. To investigate this question, we employed human post-mortem retinas and transgenic rd1_Opto-mGluR6 mice expressing the optogenetic construct Opto-mGluR6 in ON-bipolar cells and carrying the retinal degeneration rd1 mutation. We found significant changes in delayed rectifier potassium channel expression in ON-bipolar cells of degenerative retinas. In particular, we found an increase in Kv1.3 expression already in early stages of degeneration. Immunohistochemistry localized Kv1.3 channels specifically to OBC axons. In whole-cell patch-clamp experiments, ON-bipolar cells in the degenerated murine retina were less responsive, which could be reversed by application of the specific Kv1.3 antagonist Psora-4. Notably, Kv1.3 block significantly increased the amplitude and kinetics of Opto-mGluR6-mediated light responses in ON-bipolar cells of the blind retina and increased the signal-to-noise ratio of light-triggered responses in retinal ganglion cells. We propose that reduction of Kv1.3 activity in the degenerated retina, either by pharmacological block or by KCNA3 gene silencing, could improve the quality of restored vision.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
