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

Oron Kotler, Yana Khrapunsky, Arik Shvartsman, Hui Dai, Leigh D. Plant, Steven A.N. Goldstein, Ilya Fleidervish

Research output: Contribution to journalArticlepeer-review

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 NaV 1.2 and NaV 1.6 channels lead to distinct contributions to AP initiation and propagation. While NaV 1.6 at the distal AIS promotes AP initiation and forward propagation, NaV 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 NaV 1.6, these effects were attributed to SUMOylation of NaV 1.2. Moreover, SUMO effects were absent in a mouse engineered to express NaV 1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of NaV 1.2 exclusively controls INaP generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.

Original languageAmerican English
Article numbere81463
JournaleLife
Volume12
DOIs
StatePublished - 1 Feb 2023

Keywords

  • I
  • Na 1.2
  • SENP
  • SUMO
  • action potential
  • axon initial segment
  • backpropagation
  • layer 5 pyramidal neurons
  • neuronal excitability

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience

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