SUMOylation of Na1.2 Channels Regulates the Velocity of Backpropagating Action Potentials in Cortical Pyramidal Neurons

Overview

Journal Elife

Specialty Biology

Date 2023 Feb 16

PMID 36794908

Authors

Oron Kotler

Yana Khrapunsky

Arik Shvartsman

Hui Dai

Leigh D Plant

Steven A N Goldstein

Ilya Fleidervish

Affiliations

Soon will be listed here.

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 Na1.2 and Na1.6 channels lead to distinct contributions to AP initiation and propagation. While Na1.6 at the distal AIS promotes AP initiation and forward propagation, Na1.2 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 Na1.6, these effects were attributed to SUMOylation of Na1.2. Moreover, SUMO effects were absent in a mouse engineered to express Na1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of Na1.2 exclusively controls I generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.

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