Altered sarcoplasmic reticulum (SR) Ca$^2+$-ATPase and Na$^+$-Ca$^2+$
exchange (NCX) function have been implicated in depressing SR Ca$^2+$
content and contractile function in heart failure (HF). Enhanced
diastolic ryanodine receptor (RyR) leak could also lower SR Ca$^2+$
load in HF, but direct cellular measurements are lacking. In this
study, we measure SR Ca$^2+$ leak directly in intact isolated
rabbit ventricular myocytes from a well-developed nonischemic HF
model. Abrupt block of SR Ca$^2+$ leak by tetracaine shifts Ca$^2+$
from the cytosol to SR. The tetracaine-induced decline in Ca$^2+$i
and increase total SR Ca$^2+$ load (Ca$^2+$SRT) directly
indicate the SR Ca$^2+$ leak (before tetracaine). Diastolic SR
Ca$^2+$ leak increases with Ca$^2+$SRT, and for any Ca$^2+$SRT
is greater in HF versus control. Mathematical modeling was used to
compare the relative impact of alterations in SR Ca$^2+$ leak,
SR Ca$^2+$-ATPase, and Na$^+$-Ca$^2+$ exchange on SR
Ca$^2+$ load in HF. We conclude that increased diastolic SR Ca$^2+$
leak in HF may contribute to reductions in SR Ca$^2+$ content,
but changes in NCX in this HF model have more impact on Ca$^2+$SRT.
%0 Journal Article
%1 Shan_2003_592
%A Shannon, Thomas R
%A Pogwizd, Steven M
%A Bers, Donald M
%D 2003
%J Circ. Res.
%K 12946948 Action Animals, Calcium Calcium, Cardiac, Cardiovascular, Cell Computer Congestive, Contraction, Cytosol, Failure, Gov't, Heart Humans, Ion Membrane Membrane, Models, Myocardial Myocardium, Myocytes, Non-U.S. P.H.S., Potentials, Rabbits, Research Reticulum, Sarcoplasmic Signaling, Simulation, Support, Tetracaine, Transport, U.S. Ventricles,
%N 7
%P 592--594
%R 10.1161/01.RES.0000093399.11734.B3
%T Elevated sarcoplasmic reticulum Ca$^2+$ leak in intact ventricular
myocytes from rabbits in heart failure.
%U http://dx.doi.org/10.1161/01.RES.0000093399.11734.B3
%V 93
%X Altered sarcoplasmic reticulum (SR) Ca$^2+$-ATPase and Na$^+$-Ca$^2+$
exchange (NCX) function have been implicated in depressing SR Ca$^2+$
content and contractile function in heart failure (HF). Enhanced
diastolic ryanodine receptor (RyR) leak could also lower SR Ca$^2+$
load in HF, but direct cellular measurements are lacking. In this
study, we measure SR Ca$^2+$ leak directly in intact isolated
rabbit ventricular myocytes from a well-developed nonischemic HF
model. Abrupt block of SR Ca$^2+$ leak by tetracaine shifts Ca$^2+$
from the cytosol to SR. The tetracaine-induced decline in Ca$^2+$i
and increase total SR Ca$^2+$ load (Ca$^2+$SRT) directly
indicate the SR Ca$^2+$ leak (before tetracaine). Diastolic SR
Ca$^2+$ leak increases with Ca$^2+$SRT, and for any Ca$^2+$SRT
is greater in HF versus control. Mathematical modeling was used to
compare the relative impact of alterations in SR Ca$^2+$ leak,
SR Ca$^2+$-ATPase, and Na$^+$-Ca$^2+$ exchange on SR
Ca$^2+$ load in HF. We conclude that increased diastolic SR Ca$^2+$
leak in HF may contribute to reductions in SR Ca$^2+$ content,
but changes in NCX in this HF model have more impact on Ca$^2+$SRT.
@article{Shan_2003_592,
abstract = {Altered sarcoplasmic reticulum (SR) {C}a$^{2+}$-ATPase and {N}a$^{+}$-{C}a$^{2+}$
exchange (NCX) function have been implicated in depressing SR {C}a$^{2+}$
content and contractile function in heart failure (HF). Enhanced
diastolic ryanodine receptor (RyR) leak could also lower SR {C}a$^{2+}$
load in HF, but direct cellular measurements are lacking. In this
study, we measure SR {C}a$^{2+}$ leak directly in intact isolated
rabbit ventricular myocytes from a well-developed nonischemic HF
model. Abrupt block of SR {C}a$^{2+}$ leak by tetracaine shifts {C}a$^{2+}$
from the cytosol to SR. The tetracaine-induced decline in [{C}a$^{2+}$]i
and increase total SR {C}a$^{2+}$ load ([{C}a$^{2+}$]{SRT}) directly
indicate the SR {C}a$^{2+}$ leak (before tetracaine). Diastolic SR
{C}a$^{2+}$ leak increases with [{C}a$^{2+}$]{SRT}, and for any [{C}a$^{2+}$]{SRT}
is greater in HF versus control. Mathematical modeling was used to
compare the relative impact of alterations in SR {C}a$^{2+}$ leak,
SR {C}a$^{2+}$-ATPase, and {N}a$^{+}$-{C}a$^{2+}$ exchange on SR
{C}a$^{2+}$ load in HF. We conclude that increased diastolic SR {C}a$^{2+}$
leak in HF may contribute to reductions in SR {C}a$^{2+}$ content,
but changes in NCX in this HF model have more impact on [{C}a$^{2+}$]{SRT}.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Shannon, Thomas R and Pogwizd, Steven M and Bers, Donald M},
biburl = {https://www.bibsonomy.org/bibtex/20b6b8bf4599a73324253f66a35070d72/hake},
description = {The whole bibliography file I use.},
doi = {10.1161/01.RES.0000093399.11734.B3},
file = {Shan_2003_592.pdf:Shan_2003_592.pdf:PDF},
interhash = {e05d989023982b301b9497cb109e81ea},
intrahash = {0b6b8bf4599a73324253f66a35070d72},
journal = {Circ. Res.},
key = 106,
keywords = {12946948 Action Animals, Calcium Calcium, Cardiac, Cardiovascular, Cell Computer Congestive, Contraction, Cytosol, Failure, Gov't, Heart Humans, Ion Membrane Membrane, Models, Myocardial Myocardium, Myocytes, Non-U.S. P.H.S., Potentials, Rabbits, Research Reticulum, Sarcoplasmic Signaling, Simulation, Support, Tetracaine, Transport, U.S. Ventricles,},
month = Oct,
number = 7,
pages = {592--594},
pii = {01.RES.0000093399.11734.B3},
pmid = {12946948},
timestamp = {2009-06-03T11:21:30.000+0200},
title = {Elevated sarcoplasmic reticulum {C}a$^{2+}$ leak in intact ventricular
myocytes from rabbits in heart failure.},
url = {http://dx.doi.org/10.1161/01.RES.0000093399.11734.B3},
volume = 93,
year = 2003
}