Pharmacological determination of the fractional block of Nav channels required to impair neuronal excitability and

epileptiform activity inhibition multiarray electrophysiology pharmacology sodium channel tetrodotoxin

Journal

Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935

Informations de publication

Date de publication:
2022
Historique:
received: 09 06 2022
accepted: 31 08 2022
entrez: 17 10 2022
pubmed: 18 10 2022
medline: 18 10 2022
Statut: epublish

Résumé

Voltage-gated sodium channels (Nav) are essential for the initiation and propagation of action potentials in neurons. Of the nine human channel subtypes, Nav1.1, Nav1.2 and Nav1.6 are prominently expressed in the adult central nervous system (CNS). All three of these sodium channel subtypes are sensitive to block by the neurotoxin tetrodotoxin (TTX), with TTX being almost equipotent on all three subtypes. In the present study we have used TTX to determine the fractional block of Nav channels required to impair action potential firing in pyramidal neurons and reduce network seizure-like activity. Using automated patch-clamp electrophysiology, we first determined the IC

Identifiants

pubmed: 36246527
doi: 10.3389/fncel.2022.964691
pmc: PMC9557217
doi:

Types de publication

Journal Article

Langues

eng

Pagination

964691

Informations de copyright

Copyright © 2022 Thouta, Waldbrook, Lin, Mahadevan, Mezeyova, Soriano, Versi, Goodchild and Parrish.

Déclaration de conflit d'intérêts

ST, MW, SL, AM, JM, MS, and SG are employees of Xenon Pharmaceuticals Inc. and may hold stock or stock options in the company. RP and PV were employees of Xenon Pharmaceuticals Inc.

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Auteurs

Samrat Thouta (S)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Matthew G Waldbrook (MG)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Sophia Lin (S)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Arjun Mahadevan (A)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Janette Mezeyova (J)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Maegan Soriano (M)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Pareesa Versi (P)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

Samuel J Goodchild (SJ)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.

R Ryley Parrish (RR)

Department of Cellular and Molecular Biology, Xenon Pharmaceuticals Inc., Burnaby, BC, Canada.
Department of Cell Biology and Physiology, Brigham Young University, Provo, UT, United States.

Classifications MeSH