<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Knapp, O</style></author><author><style face="normal" font="default" size="100%">Nevin, S T</style></author><author><style face="normal" font="default" size="100%">Yasuda, T</style></author><author><style face="normal" font="default" size="100%">Lawrence, N</style></author><author><style face="normal" font="default" size="100%">Lewis, R J</style></author><author><style face="normal" font="default" size="100%">Adams, D J</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Biophysical properties of Na(v) 1.8/Na(v) 1.2 chimeras and inhibition by µO-conotoxin MrVIB.</style></title><secondary-title><style face="normal" font="default" size="100%">Br J Pharmacol</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Mar 27</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">ENG</style></language><abstract><style face="normal" font="default" size="100%">Background and purpose:  Voltage-gated sodium channels are expressed primarily in excitable cells and play a pivotal role in the initiation and propagation of action potentials. Nine subtypes of the pore-forming α-subunit have been identified, each with a distinct tissue distribution, biophysical properties and sensitivity to tetrodotoxin (TTX). Na(v) 1.8, a TTX-resistant (TTX-R) subtype, is selectively expressed in sensory neurons and plays a pathophysiological role in neuropathic pain. In comparison with TTX-sensitive (TTX-S) Na(v) α-subtypes in neurons, Na(v) 1.8 is most strongly inhibited by the µO-conotoxin MrVIB from Conus marmoreus. To determine which domain confers Na(v) 1.8 α-subunit its biophysical properties and MrVIB binding, we constructed various chimeric channels incorporating sequence from Na(v) 1.8 and the TTX-S Na(v) 1.2, using a domain exchange strategy. Experimental approach:  Wild-type and chimeric Na(v) channels were expressed in Xenopus oocytes and depolarization-activated Na(+) currents were recorded using the two-electrode voltage clamp technique. Key results:  MrVIB (1 µM) reduced Na(v) 1.2 current amplitude to 69 ± 12 % whereas Na(v) 1.8 current was reduced to 31 ± 3%, confirming that MrVIB has a binding preference for Na(v) 1.8. A similar reduction in Na(+) current amplitude was observed when MrVIB was applied to chimeras containing the region extending from S6 segment of domain I through the S5-S6 linker of domain II of Na(v) 1.8. In contrast, MrVIB had only a small effect on Na(+) current for chimeras containing the corresponding region of Na(v) 1.2. Conclusions and implications:  Taken together, these results suggest that domain II of Na(v) 1.8 is an important determinant of MrVIB affinity, highlighting a region of the α-subunit that may allow further nociceptor-specific ligand targeting. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22452751?dopt=Abstract</style></custom1></record></records></xml>