The Journal of General Physiology
Sign up for e-mail content alerts
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 277K)
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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eaholtz, G.
Right arrow Articles by Catterall, W. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eaholtz, G.
Right arrow Articles by Catterall, W. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*(L)-METHIONINE
*(L)-PHENYLALANINE
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?
© The Rockefeller University Press, 0022-1295/1998//75/ $5.00
Journal of General Physiology, Volume 111, Number 1, 1998

Article

Kinetic Analysis of Block of Open Sodium Channels by a Peptide Containing the Isoleucine, Phenylalanine, and Methionine (IFM) Motif from the Inactivation Gate

Galen Eaholtz*, William N. Zagotta{ddagger},§, and William A. Catterall||

From the * Graduate Program in Neurobiology, {ddagger} Department of Physiology and Biophysics, § Howard Hughes Medical Institute, and || Department of Pharmacology, University of Washington, Seattle, Washington 98195

We analyzed the kinetics of interaction between the peptide KIFMK, containing the isoleucine, phen-ylalanine, and methionine (IFM) motif from the inactivation gate, and the brain type IIA sodium channels with a mutation that disrupts inactivation (F1489Q). The on-rate constant was concentration dependent, consistent with a bimolecular reaction with open sodium channels, while the off rates were unaffected by changes in the KIFMK concentration. The apparent Kd was ~33 µM at 0 mV. The on rates were voltage dependent, supporting the hypothesis that one or both of the charges in KIFMK enter the membrane electric field. The voltage dependence of block was consistent with the equivalent movement of ~0.6 electronic charges across the membrane. In contrast, the off rates were voltage independent. The results are consistent with the hypothesis that the KIFMK peptide enters the pore of the open sodium channel from the intracellular side and blocks it.

Key Words: Voltage-dependent gating • inactivation • sodium channel • peptide

Address correspondence to William A. Catterall, Ph.D., Chairman, Department of Pharmacology, University of Washington School of Medicine, Box 357280, F-427 Health Sciences, Seattle, WA 98195-7280. Fax: 206-543-3882; E-mail: wcatt{at}u.washington.edu


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?




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