title: Role of auxiliary beta1-, beta2-, and beta3-subunits and their interaction with Na(v)1.8 voltage-gated sodium channel.
abstract: The nociceptive C-fibers of the dorsal root ganglion express several sodium channel isoforms that associate with one or more regulatory beta-subunits (beta1-beta4). To determine the effects of individual and combinations of the beta-subunit isoforms, we co-expressed Nav1.8 in combination with these beta-subunits in Xenopus oocytes. Whole-cell inward sodium currents were recorded using the two-microelectrode voltage clamp method. Our studies revealed that the co-expression beta1 alone or in combination with other beta-subunits enhanced current amplitudes, accelerated current decay kinetics, and negatively shifted the steady-state curves. In contrast, beta2 alone and in combination with beta1 altered steady-state inactivation of Nav1.8 to more depolarized potentials. Co-expression of beta3 shifted steady-state inactivation to more depolarized potentials; however, combined beta1beta3 expression caused no shift in channel availability. The results in this study suggest that the functional behavior of Nav1.8 will vary depending on the type of beta-subunit that expressed under normal and disease states.
authors.affiliation: Department of Medicine, Laval University, 2725 Chemin Sainte-Foy, Sainte-Foy, Que. G1V 4G5, Canada.
authors.forename: Kausalia
authors.initials: K
authors.lastname: Vijayaragavan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Powell
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Kinghorn
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chahine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568319:Scn10a protein, rat; D015222:Sodium Channels