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 ArticleTOXICOLOGY

Actions of Pyrethroid Insecticides on Sodium Currents, Action Potentials, and Contractile Rhythm in Isolated Mammalian Ventricular Myocytes and Perfused Hearts

C. Ian Spencer, Kathryn H. Yuill, John J. Borg, Jules C. Hancox and Roland Z. Kozlowski
Journal of Pharmacology and Experimental Therapeutics September 2001, 298 (3) 1067-1082;
C. Ian Spencer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathryn H. Yuill
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John J. Borg
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jules C. Hancox
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roland Z. Kozlowski
  • 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

This article has a correction. Please see:

  • Correction to “Actions of pyrethroid insecticides on sodium currents, action potentials, and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts” - October 01, 2001

Abstract

Pyrethroid insecticides are known to modify neuronal sodium channels, inducing persistent, steady-state sodium current at depolarized membrane potentials. Cardiac myocytes are also rich in sodium channels but comparatively little is known about the effect of pyrethroids on the heart, or on the cardiac sodium channel isoform. In the present study therefore, we determined the actions of type I and type II pyrethroids against rat and guinea pig ventricular myocytes under current and voltage clamp, and on isolated perfused rat hearts. In myocytes, tefluthrin (type I) and fenpropathrin and α-cypermethrin (type II) prolonged action potentials and evoked afterdepolarizations. The time course of sodium current (INa) was also prolonged by these compounds. Pyrethroids delayed INa inactivation, when measured under selective conditions as current sensitive to 30 μM tetrodotoxin, by increasing the proportion of slowly inactivating current at the expense of fast inactivating current. Further experiments, focusing on fenpropathrin, revealed that its effects on INa inactivation time course were dose-dependent, and the Na+ “window-current” was increased in its presence. In unstimulated, isolated hearts perfused with the same pyrethroids, the variability in contraction amplitude increased due to variations in the intervals between heartbeats. These potentially arrhythmogenic changes are consistent with the effects observed at the cellular level. The type I pyrethroid tetramethrin had little effect in any of the preparations. These findings suggest that some pyrethroids possess considerable mammalian cardiac arrhythmogenic potential, the manifestation of which in vivo may depend on the route of exposure.

Footnotes

  • ↵1 Present address: Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.

  • C.I.S. and J.J.B. were kindly supported by Oxford Molecular PLC and the Medical Research Council of Great Britain. K.Y. and J.C.H. acknowledge the support of the Wellcome Trust.

  • Abbreviations:
    INa
    sodium current
    BAPTA
    1,2-bis(2-aminophenoxy)ethaneN,N,N′N′-tetraacetic acid
    TTX
    tetrodotoxin
    AP
    action potential
    APD90
    action potential duration at 90% repolarization
    TTX-S
    tetrodotoxin-sensitive
    I-V
    current-voltage
    FOC
    force of contraction
    COV
    coefficient of variation
    • Received February 26, 2001.
    • Accepted May 29, 2001.
  • 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: 298 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 3
1 Sep 2001
  • 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.
Actions of Pyrethroid Insecticides on Sodium Currents, Action Potentials, and Contractile Rhythm in Isolated Mammalian Ventricular Myocytes and Perfused Hearts
(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 ArticleTOXICOLOGY

Actions of Pyrethroid Insecticides on Sodium Currents, Action Potentials, and Contractile Rhythm in Isolated Mammalian Ventricular Myocytes and Perfused Hearts

C. Ian Spencer, Kathryn H. Yuill, John J. Borg, Jules C. Hancox and Roland Z. Kozlowski
Journal of Pharmacology and Experimental Therapeutics September 1, 2001, 298 (3) 1067-1082;

Citation Manager Formats

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

Share
Research ArticleTOXICOLOGY

Actions of Pyrethroid Insecticides on Sodium Currents, Action Potentials, and Contractile Rhythm in Isolated Mammalian Ventricular Myocytes and Perfused Hearts

C. Ian Spencer, Kathryn H. Yuill, John J. Borg, Jules C. Hancox and Roland Z. Kozlowski
Journal of Pharmacology and Experimental Therapeutics September 1, 2001, 298 (3) 1067-1082;
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

  • Nafamostat is a Potent Human Diamine Oxidase Inhibitor
  • Chemoproteomics Investigation of Testicular Toxicity with BTK Inhibitor
  • Bosentan Alters Bile Salt Disposition
Show more Toxicology

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