Regulation of Nav1.7 and Nav1.8 peripheral nervous system sodium channels by auxiliary β subunits

Abstract

Event Abstract Back to Event Regulation of Nav1.7 and Nav1.8 peripheral nervous system sodium channels by auxiliary β subunits Juan Zhao1, Cojen Ho2, Michael E. O'Leary2 and Mohamed Chahine1* 1 Le Centre de Recherche Universite Laval Robert-Giffard, Canada 2 Jefferson Medical College, United States The Nav1. 7 and Nav1. 8 Na channel isoforms are preferentially expressed in small-diameter sensory neurons of the dorsal root ganglia (DRG) where they are known to play a central role in nociception. The goal of these studies was to investigate the β subunit regulation of the Nav1.7 and Nav1.8 channels. The Na channel α and β subunits were heterologously expressed in HEK 293 cells and the functional properties assessed from whole-cell Na current recordings. Co-expressing the β3 subunit produced a hyperpolarizing shift in Nav1.7 activation (-5 mV) and slowed channel gating. The β1 subunit produced a depolarizing shift (+ 7 mV) in the midpoint of steady-state inactivation but no change in current kinetics. The β2 and β3 subunit did not alter Nav1.7 gating and none of the β subunits produced significant changes in Na current density. Co-expressing the β1 subunit increased the Nav1.8 current density 2-fold and produced hyperpolarizing shifts in both activation (-4 mV) and inactivation (-5 mV). This contrasted with the β3 subunit, which produced a 30% reduction in Nav1.8 current amplitude. The β2 and β3 subunits did not alter the gating or current density of the Nav1.8 channel. Co-expressing the β4 subunit produced hyperpolarizing shifts in the activation (-18 mV) and inactivation (-6 mV) of the Nav1.8 channel. To further investigate the contribution of the auxiliary subunits in vivo the transcripts encoding for β subunits were quantitatively measured in small-diameter sensory neurons isolated from the rat DRG. The β3 subunit is widely expressed in DRG nociceptors where it produces a hyperpolarizing shift in Nav1.7 activation and a reduction in Nav1.8 peak current amplitude. Although the β1 and β4 subunits differentially regulate the Nav1.7 and Nav1.8 channels these subunits are expressed at comparatively low levels in sensory neurons. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Neurobiology of pain and depression Citation: Zhao J, Ho C, O'Leary ME and Chahine M (2009). Regulation of Nav1.7 and Nav1.8 peripheral nervous system sodium channels by auxiliary β subunits. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.115 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Nov 2009; Published Online: 23 Nov 2009. * Correspondence: Mohamed Chahine, Le Centre de Recherche Universite Laval Robert-Giffard, Beauport, Qc G1J 2G3, Canada, Mohamed.Chahine@phc.ulaval.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Juan Zhao Cojen Ho Michael E O'Leary Mohamed Chahine Google Juan Zhao Cojen Ho Michael E O'Leary Mohamed Chahine Google Scholar Juan Zhao Cojen Ho Michael E O'Leary Mohamed Chahine PubMed Juan Zhao Cojen Ho Michael E O'Leary Mohamed Chahine Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.