The Open UniversitySkip to content
 

Elevated InsP3R expression underlies enhanced calcium fluxes and spontaneous extra-systolic calcium release events in hypertrophic cardiac myocytes

Harzheim, Dagmar; Talasila, Amarnath; Movassagh, Mehregan; Foo, Roger S-Y.; Figg, Nichola; Bootman, Martin D. and Roderick, H. Llewelyn (2010). Elevated InsP3R expression underlies enhanced calcium fluxes and spontaneous extra-systolic calcium release events in hypertrophic cardiac myocytes. Channels (Austin), 4(1) pp. 67–71.

Full text available as:
[img]
Preview
PDF (Version of Record) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (1326Kb) | Preview
DOI (Digital Object Identifier) Link: http://doi.org/10.4161/chan.4.1.10531
Google Scholar: Look up in Google Scholar

Abstract

Cardiac hypertrophy is associated with profound remodeling of Ca(2+) signaling pathways. During the early, compensated stages of hypertrophy, Ca(2+) fluxes may be enhanced to facilitate greater contraction, whereas as the hypertrophic heart decompensates, Ca(2+) homeostatic mechanisms are dysregulated leading to decreased contractility, arrhythmia and death. Although ryanodine receptor Ca(2+) release channels (RyR) on the sarcoplasmic reticulum (SR) intracellular Ca(2+) store are primarily responsible for the Ca(2+) flux that induces myocyte contraction, a role for Ca(2+) release via the inositol 1,4,5-trisphosphate receptor (InsP(3)R) in cardiac physiology has also emerged. Specifically, InsP(3)-induced Ca(2+) signals generated following myocyte stimulation with an InsP(3)-generating agonist (e.g., endothelin, ET-1), lead to modulation of Ca(2+) signals associated with excitation-contraction coupling (ECC) and the induction of spontaneous Ca(2+) release events that cause cellular arrhythmia. Using myocytes from spontaneously hypertensive rats (SHR), we recently reported that expression of the type 2 InsP(3)R (InsP(3)R2) is significantly increased during hypertrophy. Notably, this increased expression was restricted to the junctional SR in close proximity to RyRs. There, enhanced Ca(2+) release via InsP(3)Rs serves to sensitize neighboring RyRs causing an augmentation of Ca(2+) fluxes during ECC as well as an increase in non-triggered Ca(2+) release events. Although the sensitization of RyRs may be a beneficial consequence of elevated InsP(3)R expression during hypertrophy, the spontaneous Ca(2+) release events are potentially of pathological significance giving rise to cardiac arrhythmia. InsP(3)R2 expression was also increased in hypertrophic hearts from patients with ischemic dilated cardiomyopathy and aortically-banded mice demonstrating that increased InsP(3)R expression may be a general phenomenon that underlies Ca(2+) changes during hypertrophy.

Item Type: Journal Article
Copyright Holders: 2010 Landes Bioscience
ISSN: 1933-6969
Academic Unit/Department: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 34846
Depositing User: Martin Bootman
Date Deposited: 25 Oct 2012 09:37
Last Modified: 04 Aug 2016 06:29
URI: http://oro.open.ac.uk/id/eprint/34846
Share this page:

Altmetrics

Scopus Citations

Download history for this item

These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.

▼ Automated document suggestions from open access sources

Actions (login may be required)

Policies | Disclaimer

© The Open University   + 44 (0)870 333 4340   general-enquiries@open.ac.uk