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.
%0 Journal Article
%1 Song_2006_4305
%A Song, Long-Sheng
%A Sobie, Eric A
%A McCulle, Stacey
%A Lederer, W. J.
%A Balke, C. William
%A Cheng, Heping
%D 2006
%J Proc. Natl. Acad. Sci. U. S. A.
%K Animal; Animals; Calcium Cardiac; Cardiovascular; Channel Congestive; Disease Failure, Heart Inbred Models, Myocytes, Phenotype; Rats, Rats; Receptor Release Ryanodine SHR; Signaling; WKY;
%N 11
%P 4305--4310
%R 10.1073/pnas.0509324103
%T Orphaned ryanodine receptors in the failing heart.
%U http://dx.doi.org/10.1073/pnas.0509324103
%V 103
%X 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.
@article{Song_2006_4305,
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 {C}a$^{2+}$ signaling. In heart failure, multiple cellular
defects develop, including reduced contractility, altered {C}a$^{2+}$
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 {C}a$^{2+}$ signaling that are related to
restructuring of the spatial organization of the cells. Myocytes
display both a reduced ability to trigger sarcoplasmic reticulum
{C}a$^{2+}$ 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 {C}a$^{2+}$ release
channels, the ryanodine receptors (RyRs). These orphaned RyRs appear
to be responsible for the dyssynchronous {C}a$^{2+}$ sparks that
have been linked to blunted contractility and, probably, {C}a$^{2+}$-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 {C}a$^{2+}$ instability in heart
failure.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Song, Long-Sheng and Sobie, Eric A and McCulle, Stacey and Lederer, W. J. and Balke, C. William and Cheng, Heping},
biburl = {https://www.bibsonomy.org/bibtex/2e8f710448163555ce0323ab46822e304/hake},
description = {The whole bibliography file I use.},
doi = {10.1073/pnas.0509324103},
file = {Song_2006_4305.pdf:Song_2006_4305.pdf:PDF},
interhash = {2187b83ed4cc6fdb29dd6a73c357716f},
intrahash = {e8f710448163555ce0323ab46822e304},
journal = {Proc. Natl. Acad. Sci. U. S. A.},
keywords = {Animal; Animals; Calcium Cardiac; Cardiovascular; Channel Congestive; Disease Failure, Heart Inbred Models, Myocytes, Phenotype; Rats, Rats; Receptor Release Ryanodine SHR; Signaling; WKY;},
month = Mar,
number = 11,
pages = {4305--4310},
pii = {0509324103},
pmid = {16537526},
timestamp = {2009-06-03T11:21:32.000+0200},
title = {Orphaned ryanodine receptors in the failing heart.},
url = {http://dx.doi.org/10.1073/pnas.0509324103},
volume = 103,
year = 2006
}