SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
- Ben-Gurion University of the Negev, Israel
- University of California, Irvine, United States
- Northeastern University, United States
Abstract
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 NaV1.2 and NaV1.6 channels lead to distinct contributions to AP initiation and propagation. While NaV1.6 at the distal AIS promotes AP initiation and forward propagation, NaV1.2 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 NaV1.6, these effects were attributed to SUMOylation of NaV1.2. Moreover, SUMO effects were absent in a mouse engineered to express NaV1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of NaV1.2 exclusively controls INaP generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting file; the Source Data files will be uploaded to the Dryad server promptly
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SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neuronsDryad Digital Repository, doi:10.5061/dryad.tx95x6b1g.
Article and author information
Author details
Steven AN Goldstein
Funding
Israel Science Foundation (1384/19)
- Ilya Fleidervish
National Institutes of Health (R01HL10549)
- Steven AN Goldstein
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was carried out at the Ben-Gurion University of the Negev in accordance with the recommendations of guidelines for the welfare of experimental animals. Animal experiments were approved by the Institutional Animal Care and Use Committee of Ben-Gurion University (protocols IL-68-09-2019(A), IL-79-10-2020(D)).
Copyright
© 2023, Kotler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
eLife 12:e81463.
https://doi.org/10.7554/eLife.81463
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