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SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons

Voltage-gated sodium channels located in axon initial segments (AIS) trigger action potentials (AP) and play pivotal roles in the excitability of cortical pyramidal neurons. The differential electrophysiological properties and distributions of Na(V)1.2 and Na(V)1.6 channels lead to distinct contribu...

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Autores principales: Kotler, Oron, Khrapunsky, Yana, Shvartsman, Arik, Dai, Hui, Plant, Leigh D, Goldstein, Steven AN, Fleidervish, Ilya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014073/
https://www.ncbi.nlm.nih.gov/pubmed/36794908
http://dx.doi.org/10.7554/eLife.81463
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author Kotler, Oron
Khrapunsky, Yana
Shvartsman, Arik
Dai, Hui
Plant, Leigh D
Goldstein, Steven AN
Fleidervish, Ilya
author_facet Kotler, Oron
Khrapunsky, Yana
Shvartsman, Arik
Dai, Hui
Plant, Leigh D
Goldstein, Steven AN
Fleidervish, Ilya
author_sort Kotler, Oron
collection PubMed
description Voltage-gated sodium channels located in axon initial segments (AIS) trigger action potentials (AP) and play pivotal roles in the excitability of cortical pyramidal neurons. The differential electrophysiological properties and distributions of Na(V)1.2 and Na(V)1.6 channels lead to distinct contributions to AP initiation and propagation. While Na(V)1.6 at the distal AIS promotes AP initiation and forward propagation, Na(V)1.2 at the proximal AIS promotes the backpropagation of APs to the soma. Here, we show the small ubiquitin-like modifier (SUMO) pathway modulates Na(+) channels at the AIS to increase neuronal gain and the speed of backpropagation. Since SUMO does not affect Na(V)1.6, these effects were attributed to SUMOylation of Na(V)1.2. Moreover, SUMO effects were absent in a mouse engineered to express Na(V)1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of Na(V)1.2 exclusively controls I(NaP) generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.
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spelling pubmed-100140732023-03-15 SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons Kotler, Oron Khrapunsky, Yana Shvartsman, Arik Dai, Hui Plant, Leigh D Goldstein, Steven AN Fleidervish, Ilya eLife Neuroscience Voltage-gated sodium channels located in axon initial segments (AIS) trigger action potentials (AP) and play pivotal roles in the excitability of cortical pyramidal neurons. The differential electrophysiological properties and distributions of Na(V)1.2 and Na(V)1.6 channels lead to distinct contributions to AP initiation and propagation. While Na(V)1.6 at the distal AIS promotes AP initiation and forward propagation, Na(V)1.2 at the proximal AIS promotes the backpropagation of APs to the soma. Here, we show the small ubiquitin-like modifier (SUMO) pathway modulates Na(+) channels at the AIS to increase neuronal gain and the speed of backpropagation. Since SUMO does not affect Na(V)1.6, these effects were attributed to SUMOylation of Na(V)1.2. Moreover, SUMO effects were absent in a mouse engineered to express Na(V)1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of Na(V)1.2 exclusively controls I(NaP) generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity. eLife Sciences Publications, Ltd 2023-02-16 /pmc/articles/PMC10014073/ /pubmed/36794908 http://dx.doi.org/10.7554/eLife.81463 Text en © 2023, Kotler et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Kotler, Oron
Khrapunsky, Yana
Shvartsman, Arik
Dai, Hui
Plant, Leigh D
Goldstein, Steven AN
Fleidervish, Ilya
SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
title SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
title_full SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
title_fullStr SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
title_full_unstemmed SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
title_short SUMOylation of Na(V)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
title_sort sumoylation of na(v)1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014073/
https://www.ncbi.nlm.nih.gov/pubmed/36794908
http://dx.doi.org/10.7554/eLife.81463
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