The Journal of General Physiology
Cell MicroControls
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online Jun 26 2006. doi:10.1085/jgp.200609492
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 128, Number 1, 119-132
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1762K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JGP
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sack, J. T.
Right arrow Articles by Aldrich, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sack, J. T.
Right arrow Articles by Aldrich, R. W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

 Binding of a Gating Modifier Toxin Induces Intersubunit Cooperativity Early in the Shaker K Channel's Activation Pathway



Jon T. Sack and Richard W. Aldrich

Howard Hughes Medical Institute and Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305

Correspondence to Richard W. Aldrich: raldrich{at}mail.utexas.edu

Potassium currents from voltage-gated Shaker K channels activate with a sigmoid rise. The degree of sigmoidicity in channel opening kinetics confirms that each subunit of the homotetrameric Shaker channel undergoes more than one conformational change before the channel opens. We have examined effects of two externally applied gating modifiers that reduce the sigmoidicity of channel opening. A toxin from gastropod mucus, 6-bromo-2-mercaptotryptamine (BrMT), and divalent zinc are both found to slow the same conformational changes early in Shaker's activation pathway. Sigmoidicity measurements suggest that zinc slows a conformational change independently in each channel subunit. Analysis of activation in BrMT reveals cooperativity among subunits during these same early steps. A lack of competition with either agitoxin or tetraethylammonium indicates that BrMT binds channel subunits outside of the external pore region in an allosterically cooperative fashion. Simulations including negatively cooperative BrMT binding account for its ability to induce gating cooperativity during activation. We conclude that cooperativity among K channel subunits can be greatly altered by experimental conditions.

Abbreviation used in this paper: BrMT, 6-bromo- 2-mercaptotryptamine.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 JGPHome page
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]

Home page
 JGPHome page
F. V. Campos, B. Chanda, P. S.L. Beirao, and F. Bezanilla
{beta}-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
J. Gen. Physiol., August 27, 2007; 130(3): 257 - 268.
[Abstract] [Full Text] [PDF]


  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents