Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • 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
  • My Cart

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
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

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

Inhibitory Effects of Vesnarinone on Cloned Cardiac Delayed Rectifier K+ Channels Expressed in a Mammalian Cell Line

Yusuke Katayama, Akikazu Fujita, Tohru Ohe, Ian Findlay and Yoshihisa Kurachi
Journal of Pharmacology and Experimental Therapeutics July 2000, 294 (1) 339-346;
Yusuke Katayama
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akikazu Fujita
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tohru Ohe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian Findlay
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshihisa Kurachi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Vesnarinone, a phosphodiesterase inhibitor, prolongs cardiac action potential duration by inhibiting the delayed rectifier K+current, IK. We examined the effect of this agent on human ether-a-go-go related gene (HERG) and KvLQT1/minK K+ channels heterologously expressed in human embryonic kidney 293T cells with the whole-cell patch-clamp technique. HERG channel current was inhibited by vesnarinone in a concentration-dependent manner, whereas KvLQT1/minK current was hardly affected by the drug. The inhibition of HERG current by vesnarinone became more prominent and faster as the membrane potential was more depolarized. The properties of inhibition could be described by a first order reaction between the drug and the channel that was apparently independent of HERG channel gating. Although the unbinding rate constant of the drug was constant, the apparent binding rate constant increased as the membrane was more depolarized and the drug concentration was raised. This model also could explain the fast recovery from the drug's effect at hyperpolarized potentials and its rate-dependent inhibition of HERG. Therefore, the effect of vesnarinone on the HERG-K+ current could be adequately described by a simple kinetic model of drug-channel interaction.

Footnotes

  • Send reprint requests to: Dr. Yoshihisa Kurachi, Department of Pharmacology II, Faculty of Medicine & Graduate School of Medicine, A7, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail:ykurachi{at}pharma2.med.osaka-u.ac.jp

  • Abbreviations:
    PDE
    phosphodiesterase
    IK
    cardiac delayed rectifier K+current
    IKr
    rapidly activating component of cardiac delayed rectifier K+ current
    IKs
    slowly activating component of cardiac delayed rectifier K+ current
    HERG
    humanether-a-go-go related gene
    MiRP1
    minK-related peptide 1
    I-V
    current-voltage
    • Received December 27, 1999.
    • Accepted March 16, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 294 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 1
1 Jul 2000
  • Table of Contents
  • About the Cover
  • Index by author
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.
Inhibitory Effects of Vesnarinone on Cloned Cardiac Delayed Rectifier K+ Channels Expressed in a Mammalian Cell Line
(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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCARDIOVASCULAR

Inhibitory Effects of Vesnarinone on Cloned Cardiac Delayed Rectifier K+ Channels Expressed in a Mammalian Cell Line

Yusuke Katayama, Akikazu Fujita, Tohru Ohe, Ian Findlay and Yoshihisa Kurachi
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 339-346;

Citation Manager Formats

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

Share
Research ArticleCARDIOVASCULAR

Inhibitory Effects of Vesnarinone on Cloned Cardiac Delayed Rectifier K+ Channels Expressed in a Mammalian Cell Line

Yusuke Katayama, Akikazu Fujita, Tohru Ohe, Ian Findlay and Yoshihisa Kurachi
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 339-346;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Optimized S-nitrosohemoglobin Synthesis in Red Blood Cells
  • Exosomal miRNAs drive thrombosis in COVID-19
  • mitochondrial miRs in Fabry disease
Show more Cardiovascular

Similar Articles

Advertisement
  • 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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics