Planned intervention: On Wednesday April 3rd 05:30 UTC Zenodo will be unavailable for up to 2-10 minutes to perform a storage cluster upgrade.
Published February 23, 2023 | Version v1
Dataset Open

SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons

  • 1. Ben-Gurion University of the Negev
  • 2. University of California, Irvine
  • 3. Northeastern University

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 NaV1.2 and NaV1.6 channels lead to distinct contributions to AP initiation and backpropagation.  While NaV1.6 at the distal AIS promotes AP initiation and forward propagation, NaV1.2 at the proximal AIS promotes backpropagation of APs to the soma.  Here, we show the Small Ubiquitin-like Modifier (SUMO) pathway modulates persistent sodium current (INaP) generation 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.

Notes

Electrical recordings (PClamp 9, Microcal Origin 6)

Fast fluorescence imaging (Neuroplex, RedShirt Imaging)

Compartmental modeling (Neuron, Yale)

Funding provided by: Israel Science Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100003977
Award Number: 1384/19

Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: R01HL10549

Files

CC_Electrical_data.zip

Files (9.1 GB)

Name Size Download all
md5:f6a180f694df226f7cc929c24f5ce2bf
239.7 MB Preview Download
md5:381b93608dbe3677cbd250690a54f9ab
1.1 GB Preview Download
md5:db249da8e7e192cef5358b604b35d840
29.2 kB Preview Download
md5:544c2e3b07647644944a2ddcad065469
229.5 kB Preview Download
md5:19d010944bfd3e50a42f494b8aef1f11
54.3 MB Preview Download
md5:ad6c0028563a818c617771e795aecfd5
7.7 GB Preview Download