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Updated: May 20, 2026

Use of Primary Cultured Hippocampal Neurons to Study the Assembly of Axon Initial Segments
Published on: February 12, 2021
GSK3 and β-catenin determines functional expression of sodium channels at the axon initial segment
Mónica Tapia1, Ana Del Puerto, Alberto Puime
1Department of Cellular, Molecular and Developmental Neurobiology, Instituto Cajal, CSIC, Avenida Doctor Arce, Madrid, 28002, Spain.
Abstract:
Neuronal action potentials are generated through voltage-gated sodium channels, which are tethered by ankyrinG at the membrane of the axon initial segment (AIS). Despite the importance of the AIS in the control of neuronal excitability, the cellular and molecular mechanisms regulating sodium channel expression at the AIS remain elusive. Our results show that GSK3α/β and β-catenin phosphorylated by GSK3 (S33/37/T41) are localized at the AIS and are new components of this essential neuronal domain. Pharmacological inhibition of GSK3 or β-catenin knockdown with shRNAs decreased the levels of phosphorylated-β-catenin, ankyrinG, and voltage-gated sodium channels at the AIS, both "in vitro" and "in vivo", therefore diminishing neuronal excitability as evaluated via sodium current amplitude and action potential number. Thus, our results suggest a mechanism for the modulation of neuronal excitability through the control of sodium channel density by GSK3 and β-catenin at the AIS.
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