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 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

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

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off