Modulation of human Nav1.7 channel gating by synthetic alpha-scorpion toxin OD1 and its analogs

Motin, Leonid, Durek, Thomas and Adams, David J. (2016) Modulation of human Nav1.7 channel gating by synthetic alpha-scorpion toxin OD1 and its analogs. Channels, 10 2: 139-147. doi:10.1080/19336950.2015.1120392


Author Motin, Leonid
Durek, Thomas
Adams, David J.
Title Modulation of human Nav1.7 channel gating by synthetic alpha-scorpion toxin OD1 and its analogs
Formatted title
Modulation of human Nav1.7 channel gating by synthetic alpha-scorpion toxin OD1 and its analogs
Journal name Channels   Check publisher's open access policy
ISSN 1933-6950
1933-6969
Publication date 2016-03
Year available 2015
Sub-type Article (original research)
DOI 10.1080/19336950.2015.1120392
Open Access Status Not Open Access
Volume 10
Issue 2
Start page 139
End page 147
Total pages 9
Place of publication Philadelphia, PA United States
Publisher Taylor & Francis
Collection year 2016
Language eng
Formatted abstract
Nine different voltage-gated sodium channel isoforms are responsible for inducing and propagating action potentials in the mammalian nervous system. The Nav1.7 channel isoform plays an important role in conducting nociceptive signals. Specific mutations of this isoform may impair gating behavior of the channel resulting in several pain syndromes. In addition to channel mutations, similar or opposite changes in gating may be produced by spider and scorpion toxins binding to different parts of the voltage-gated sodium channel. In the present study, we analyzed the effects of the α-scorpion toxin OD1 and 2 synthetic toxin analogs on the gating properties of the Nav1.7 sodium channel. All toxins potently inhibited channel inactivation, however, both toxin analogs showed substantially increased potency by more than one order of magnitude when compared with that of wild-type OD1. The decay phase of the whole-cell Na+ current was substantially slower in the presence of toxins than in their absence. Single-channel recordings in the presence of the toxins revealed that Na+ current inactivation slowed due to prolonged flickering of the channel between open and closed states. Our findings support the voltage-sensor trapping model of α-scorpion toxin action, in which the toxin prevents a conformational change in the domain IV voltage sensor that normally leads to fast channel inactivation.
Keyword Gating
Nav1.7
Patch clamp
Scorpion toxin
Voltage-gated sodium channel
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Advanced Studies in the Humanities
 
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