Orphaned ryanodine receptors in the failing heart

Long-Sheng Song; Eric A Sobie; Stacey McCulle; W J Lederer; C William Balke; Heping Cheng

doi:10.1073/pnas.0509324103

Back

Orphaned ryanodine receptors in the failing heart

Journal article

Open access

Peer reviewed

Orphaned ryanodine receptors in the failing heart

Long-Sheng Song, Eric A Sobie, Stacey McCulle, W J Lederer, C William Balke and Heping Cheng

Proceedings of the National Academy of Sciences - PNAS, Vol.103(11), pp.4305-4310

03/14/2006

DOI: 10.1073/pnas.0509324103

PMCID: PMC1449688

PMID: 16537526

Files and links (1)

url

https://doi.org/10.1073/pnas.0509324103View

Published (Version of record) Open Access

Abstract

Heart muscle is characterized by a regular array of proteins and structures that form a repeating functional unit identified as the sarcomere. This regular structure enables tight coupling between electrical activity and Ca(2+) signaling. In heart failure, multiple cellular defects develop, including reduced contractility, altered Ca(2+) signaling, and arrhythmias; however, the underlying causes of these defects are not well understood. Here, in ventricular myocytes from spontaneously hypertensive rats that develop heart failure, we identify fundamental changes in Ca(2+) signaling that are related to restructuring of the spatial organization of the cells. Myocytes display both a reduced ability to trigger sarcoplasmic reticulum Ca(2+) release and increased spatial dispersion of the transverse tubules (TTs). Remodeled TTs in cells from failing hearts no longer exist in the regularly organized structures found in normal heart cells, instead moving within the sarcomere away from the Z-line structures and leaving behind the sarcoplasmic reticulum Ca(2+) release channels, the ryanodine receptors (RyRs). These orphaned RyRs appear to be responsible for the dyssynchronous Ca(2+) sparks that have been linked to blunted contractility and, probably, Ca(2+)-dependent arrhythmias in diverse models of heart failure. We conclude that the increased spatial dispersion of the TTs and orphaned RyRs lead to the loss of local control and Ca(2+) instability in heart failure.

Rats, Inbred SHR

Models, Cardiovascular

Rats

Rats, Inbred WKY

Ryanodine Receptor Calcium Release Channel - metabolism

Heart Failure - metabolism

Heart Failure - pathology

Myocytes, Cardiac - pathology

Phenotype

Animals

Myocytes, Cardiac - metabolism

Calcium Signaling

Disease Models, Animal

Details

Title: Subtitle: Orphaned ryanodine receptors in the failing heart
Creators: Long-Sheng Song - Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA. songl@umbi.umd.edu
Eric A Sobie
Stacey McCulle
W J Lederer
C William Balke
Heping Cheng
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.103(11), pp.4305-4310
DOI: 10.1073/pnas.0509324103
PMID: 16537526
PMCID: PMC1449688
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Grant note: R01 HL076230 / NHLBI NIH HHS
Language: English
Date published: 03/14/2006
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094666402771

Metrics

35 Record Views

379 Times Cited - Web of Science