Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Abstract

Selective inhibition of potassium currents in rat ventricle by clofilium and its tertiary homolog.

N A Castle
Journal of Pharmacology and Experimental Therapeutics April 1991, 257 (1) 342-350;
N A Castle
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The effects of clofilium and its tertiary homolog, LY97119 (LY), on K+ currents in isolated ventricular myocytes from adult rat were examined using the whole-cell patch-clamp technique. Acute exposure (less than 30 min) to high concentrations of clofilium (30-100 microM) produced a slowly developing reduction in the peak of the transient outward current (Ito) and an apparent increase in the rate of current inactivation. In addition, inhibition exhibited a marked dependence on the frequency of stimulation (i.e., use-dependent inhibition). For "short" exposure times (i.e., less than 30 min), steady-state inhibition was not attained. Therefore, myocytes were preincubated with clofilium for at least 3 hr before use. Under these conditions, the median inhibitory concentration for steady-state use-dependent inhibition of Ito was 0.5 microM. Recovery of Ito from use-dependent inhibition followed a biexponential time course; tau fast = 75 msec, tau slow = 17 sec. The relative magnitude of the slow component (but not its time constant) increased with higher clofilium concentrations. LY, like clofilium, also induced a time-dependent inhibition of Ito (median inhibiting concentration 0.9 microM). However, unlike clofilium, steady state with LY was reached within 5 min. Furthermore, LY (3 microM) produced very little use-dependent inhibition (29% at 1 Hz compared with 92% for clofilium). This is possibly due to a "fast" unbinding rate upon repolarization (tau = 1.8 s). In contrast to clofilium, LY (1-10 microM) also inhibited the inward rectifier (IK1). The present results suggest that inhibition of Ito may contribute to clofilium's class III antiarrhythmic action.

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics
Vol. 257, Issue 1
1 Apr 1991
  • Table of Contents
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Selective inhibition of potassium currents in rat ventricle by clofilium and its tertiary homolog.
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
Citation Tools
Abstract

Selective inhibition of potassium currents in rat ventricle by clofilium and its tertiary homolog.

N A Castle
Journal of Pharmacology and Experimental Therapeutics April 1, 1991, 257 (1) 342-350;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Abstract

Selective inhibition of potassium currents in rat ventricle by clofilium and its tertiary homolog.

N A Castle
Journal of Pharmacology and Experimental Therapeutics April 1, 1991, 257 (1) 342-350;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2019 by the American Society for Pharmacology and Experimental Therapeutics