Ryanodine‐receptor inhibition by dantrolene effectively suppresses ventricular arrhythmias in an ex vivo model of long‐QT syndrome

Ryanodine‐receptor inhibition by dantrolene effectively suppresses ventricular arrhythmias in... 1INTRODUCTIONCellular calcium handling plays an important role in the origination of ventricular arrhythmias. Calcium overload is regarded as a major proarrhythmic factor in different entities of arrhythmias as it may lead to a prolongation of action potential duration and thereby induce early and delayed afterdepolarizations. Destabilization of the ryanodine receptor 2 (RYR2) closed state may increase the intracellular calcium level by releasing calcium from the sarcoplasmic reticulum. Activity of RYR2 is mediated by phosphorylation of the receptor and may be altered in structural heart disease leading to the origination of atrial and ventricular arrhythmias. Hyperphosphorylation of RYR2 induces an increased calcium release from the sarcoplasmic reticulum. The intracellular calcium concentration can be further augmented as a result of an increased activity of the sodium‐calcium‐exchanger (NCX). An association between a hyperphosphorylated ryanodine receptor and triggered activity has also been reported in long‐QT2 syndrome (LQT2).Dantrolene, an established drug for treatment of malignant hyperthermia, has been reported to target RYR2 and may thereby improve intracellular calcium handling in the setting of chronic heart failure. In single cell experiments, dantrolene reduced the calcium leak and increased the threshold for spontaneous release of calcium from the sarcoplasmic reticulum. In addition, dantrolene represents a promising http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cardiovascular Electrophysiology Wiley

Ryanodine‐receptor inhibition by dantrolene effectively suppresses ventricular arrhythmias in an ex vivo model of long‐QT syndrome

Loading next page...
 
/lp/wiley/ryanodine-receptor-inhibition-by-dantrolene-effectively-suppresses-5mVS146WIv
Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Journal compilation © 2018 Wiley Periodicals, Inc.
ISSN
1045-3873
eISSN
1540-8167
D.O.I.
10.1111/jce.13412
Publisher site
See Article on Publisher Site

Abstract

1INTRODUCTIONCellular calcium handling plays an important role in the origination of ventricular arrhythmias. Calcium overload is regarded as a major proarrhythmic factor in different entities of arrhythmias as it may lead to a prolongation of action potential duration and thereby induce early and delayed afterdepolarizations. Destabilization of the ryanodine receptor 2 (RYR2) closed state may increase the intracellular calcium level by releasing calcium from the sarcoplasmic reticulum. Activity of RYR2 is mediated by phosphorylation of the receptor and may be altered in structural heart disease leading to the origination of atrial and ventricular arrhythmias. Hyperphosphorylation of RYR2 induces an increased calcium release from the sarcoplasmic reticulum. The intracellular calcium concentration can be further augmented as a result of an increased activity of the sodium‐calcium‐exchanger (NCX). An association between a hyperphosphorylated ryanodine receptor and triggered activity has also been reported in long‐QT2 syndrome (LQT2).Dantrolene, an established drug for treatment of malignant hyperthermia, has been reported to target RYR2 and may thereby improve intracellular calcium handling in the setting of chronic heart failure. In single cell experiments, dantrolene reduced the calcium leak and increased the threshold for spontaneous release of calcium from the sarcoplasmic reticulum. In addition, dantrolene represents a promising

Journal

Journal of Cardiovascular ElectrophysiologyWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial