scholarly journals Nanometer-Scale Imaging of Compartment-Specific Localization and Dynamics of Voltage-Gated Sodium Channels

2021 ◽  
Author(s):  
Hui Liu ◽  
Hong-Gang Wang ◽  
Geoffrey S Pitt ◽  
Zhe Liu

Membrane excitability and cell-to-cell communication in the brain are tightly regulated by diverse ion channels and receptor proteins localized to distinct membrane compartments. Currently, a major technical barrier in cellular neuroscience is lack of reliable methods to label these membrane proteins and image their sub-cellular localization and dynamics. To overcome this challenge, we devised optical imaging strategies that enable systematic characterization of subcellular composition, relative abundances and trafficking dynamics of membrane proteins at nanometer scales in cultured neurons as well as in the brain. Using these methods, we revealed exquisite developmental regulation of subcellular distributions of voltage-gated sodium channel (VGSC) Nav1.2 and Nav1.6, settling a decade long debate regarding the molecular identity of sodium channels in dendrites. In addition, we discovered a previously uncharacterized trafficking pathway that targets Nav1.2 to unmyelinated fragments in the distal axon. Myelination counteracts this pathway, facilitating the installment of Nav1.6 as the dominant VGSC in the axon. Together, these imaging approaches unveiled compartment-specific trafficking mechanisms underpinning differential membrane distributions of VGSCs and open avenues to decipher how membrane protein localization and dynamics contribute to neural computation in the brain.

2021 ◽  
Vol 12 ◽  
Author(s):  
Ibitayo Abigail Ademuwagun ◽  
Solomon Oladapo Rotimi ◽  
Steffen Syrbe ◽  
Yvonne Ukamaka Ajamma ◽  
Ezekiel Adebiyi

Genetic epilepsy occurs as a result of mutations in either a single gene or an interplay of different genes. These mutations have been detected in ion channel and non-ion channel genes. A noteworthy class of ion channel genes are the voltage gated sodium channels (VGSCs) that play key roles in the depolarization phase of action potentials in neurons. Of huge significance are SCN1A, SCN1B, SCN2A, SCN3A, and SCN8A genes that are highly expressed in the brain. Genomic studies have revealed inherited and de novo mutations in sodium channels that are linked to different forms of epilepsies. Due to the high frequency of sodium channel mutations in epilepsy, this review discusses the pathogenic mutations in the sodium channel genes that lead to epilepsy. In addition, it explores the functional studies on some known mutations and the clinical significance of VGSC mutations in the medical management of epilepsy. The understanding of these channel mutations may serve as a strong guide in making effective treatment decisions in patient management.


Author(s):  
Zhi-mei Li ◽  
Li-xia Chen ◽  
Hua Li

The article “Voltage-gated Sodium Channels and Blockers: An Overview and Where Will They Go?”, written by Zhi-mei LI, Li-xia CHEN, Hua LI, was originally published electronically on the publisher’s internet portal on December 2019 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The original article has been corrected.Corresponding authors: Li-xia CHEN, Hua LI


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