|
|
|
|
|
|
|
||
ARTICLE |
-Scorpion Toxin Impairs a Conformational Change that Leads to Fast Inactivation of Muscle Sodium Channels
Correspondence to P. Beirão: pslb{at}reitoria.ufmg.br; or F. Bezanilla: fbezanilla{at}uchicago.edu
-Scorpion toxins bind in a voltage-dependent way to site 3 of the sodium channels, which is partially formed by the loop connecting S3 and S4 segments of domain IV, slowing down fast inactivation. We have used Ts3, an -scorpion toxin from the Brazilian scorpion Tityus serrulatus, to analyze the effects of this family of toxins on the muscle sodium channels expressed in Xenopus oocytes. In the presence of Ts3 the total gating charge was reduced by 30% compared with control conditions. Ts3 accelerated the gating current kinetics, decreasing the contribution of the slow component to the ON gating current decay, indicating that S4-DIV was specifically inhibited by the toxin. In addition, Ts3 accelerated and decreased the fraction of charge in the slow component of the OFF gating current decay, which reflects an acceleration in the recovery from the fast inactivation. Site-specific fluorescence measurements indicate that Ts3 binding to the voltage-gated sodium channel eliminates one of the components of the fluorescent signal from S4-DIV. We also measured the fluorescent signals produced by the movement of the first three voltage sensors to test whether the bound Ts3 affects the movement of the other voltage sensors. While the fluorescence–voltage (F-V) relationship of domain II was only slightly affected and the F-V of domain III remained unaffected in the presence of Ts3, the toxin significantly shifted the F-V of domain I to more positive potentials, which agrees with previous studies showing a strong coupling between domains I and IV. These results are consistent with the proposed model, in which Ts3 specifically impairs the fraction of the movement of the S4-DIV that allows fast inactivation to occur at normal rates.
© 2008 Campos et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Kahn, I. Karbat, N. Ilan, L. Cohen, S. Sokolov, W. A. Catterall, D. Gordon, and M. Gurevitz Molecular Requirements for Recognition of Brain Voltage-gated Sodium Channels by Scorpion {alpha}-Toxins J. Biol. Chem., July 31, 2009; 284(31): 20684 - 20691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Muroi and B. Chanda Local Anesthetics Disrupt Energetic Coupling between the Voltage-sensing Segments of a Sodium Channel J. Gen. Physiol., December 29, 2008; 133(1): 1 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
