Channelpedia

PubMed 22763697


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK3



Title: GSK3 and β-catenin determines functional expression of sodium channels at the axon initial segment.

Authors: Mónica Tapia, Ana del Puerto, Alberto Puime, Diana Sánchez-Ponce, Laure Fronzaroli-Molinieres, Noemí Pallas-Bazarra, Edmond Carlier, Pierre Giraud, Dominique Debanne, Francisco Wandosell, Juan José Garrido

Journal, date & volume: Cell. Mol. Life Sci., 2013 Jan , 70, 105-20

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22763697


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.