Ca(2+) release from cardiac sarcoplasmic reticulum (SR) via ryanodine
receptors (RyRs) is regulated by dyadic cleft Ca(2+) and intra-SR
free Ca(2+) (Ca(2+)(SR)). Robust SR Ca(2+) release termination
is important for stable excitation-contraction coupling, and partial
Ca(2+)(SR) depletion may contribute to release termination. Here,
we investigated the regulation of SR Ca(2+) release termination of
spontaneous local SR Ca(2+) release events (Ca(2+) sparks) by Ca(2+)(SR),
release flux, and intra-SR Ca(2+) diffusion. We simultaneously measured
Ca(2+) sparks and Ca(2+) blinks (localized elementary Ca(2+)(SR)
depletions) in permeabilized ventricular cardiomyocytes over a wide
range of SR Ca(2+) loads and release fluxes. Sparks terminated via
a Ca(2+)(SR)-dependent mechanism at a fixed Ca(2+)(SR) depletion
threshold independent of the initial Ca(2+)(SR) and release flux.
Ca(2+) blink recovery depended mainly on intra-SR Ca(2+) diffusion
rather than SR Ca(2+) uptake. Therefore, the large variation in Ca(2+)
blink recovery rates at different release sites occurred because
of differences in the degree of release site interconnection within
the SR network. When SR release flux was greatly reduced, long-lasting
release events occurred from well-connected junctions. These junctions
could sustain release because local SR Ca(2+) release and Ca(2+)(SR)
refilling reached a balance, preventing Ca(2+)(SR) from depleting
to the termination threshold. Prolonged release events eventually
terminated at a steady Ca(2+)(SR), indicative of a slower, Ca(2+)(SR)-independent
termination mechanism. These results demonstrate that there is high
variability in local SR connectivity but that SR Ca(2+) release terminates
at a fixed Ca(2+)(SR) termination threshold. Thus, reliable SR
Ca(2+) release termination depends on tight RyR regulation by Ca(2+)(SR).
%0 Journal Article
%1 Zima_2008_105
%A Zima, Aleksey V
%A Picht, Eckard
%A Bers, Donald M
%A Blatter, Lothar A
%D 2008
%J Circ Res
%K ATPases, Animals; Blockers, Calcium Calcium-Transporting Cardiac, Channel Channel, Diffusion; Fluorescence; Heart Kinetics; Membrane Microscopy, Myocytes, Permeability; Potentials; Rabbits; Receptor Release Reticulum Reticulum, Ryanodine Sarcoplasmic Signaling, Ventricles, drug effects/enzymology/metabolism effects/enzymology/metabolism; effects/metabolism; effects; metabolism; pharmacology;
%N 8
%P e105--e115
%R 10.1161/CIRCRESAHA.107.183236
%T Termination of cardiac Ca2+ sparks: role of intra-SR Ca2+, release
flux, and intra-SR Ca2+ diffusion.
%U http://dx.doi.org/10.1161/CIRCRESAHA.107.183236
%V 103
%X Ca(2+) release from cardiac sarcoplasmic reticulum (SR) via ryanodine
receptors (RyRs) is regulated by dyadic cleft Ca(2+) and intra-SR
free Ca(2+) (Ca(2+)(SR)). Robust SR Ca(2+) release termination
is important for stable excitation-contraction coupling, and partial
Ca(2+)(SR) depletion may contribute to release termination. Here,
we investigated the regulation of SR Ca(2+) release termination of
spontaneous local SR Ca(2+) release events (Ca(2+) sparks) by Ca(2+)(SR),
release flux, and intra-SR Ca(2+) diffusion. We simultaneously measured
Ca(2+) sparks and Ca(2+) blinks (localized elementary Ca(2+)(SR)
depletions) in permeabilized ventricular cardiomyocytes over a wide
range of SR Ca(2+) loads and release fluxes. Sparks terminated via
a Ca(2+)(SR)-dependent mechanism at a fixed Ca(2+)(SR) depletion
threshold independent of the initial Ca(2+)(SR) and release flux.
Ca(2+) blink recovery depended mainly on intra-SR Ca(2+) diffusion
rather than SR Ca(2+) uptake. Therefore, the large variation in Ca(2+)
blink recovery rates at different release sites occurred because
of differences in the degree of release site interconnection within
the SR network. When SR release flux was greatly reduced, long-lasting
release events occurred from well-connected junctions. These junctions
could sustain release because local SR Ca(2+) release and Ca(2+)(SR)
refilling reached a balance, preventing Ca(2+)(SR) from depleting
to the termination threshold. Prolonged release events eventually
terminated at a steady Ca(2+)(SR), indicative of a slower, Ca(2+)(SR)-independent
termination mechanism. These results demonstrate that there is high
variability in local SR connectivity but that SR Ca(2+) release terminates
at a fixed Ca(2+)(SR) termination threshold. Thus, reliable SR
Ca(2+) release termination depends on tight RyR regulation by Ca(2+)(SR).
@article{Zima_2008_105,
abstract = {Ca(2+) release from cardiac sarcoplasmic reticulum (SR) via ryanodine
receptors (RyRs) is regulated by dyadic cleft [Ca(2+)] and intra-SR
free [Ca(2+)] ([Ca(2+)](SR)). Robust SR Ca(2+) release termination
is important for stable excitation-contraction coupling, and partial
[Ca(2+)](SR) depletion may contribute to release termination. Here,
we investigated the regulation of SR Ca(2+) release termination of
spontaneous local SR Ca(2+) release events (Ca(2+) sparks) by [Ca(2+)](SR),
release flux, and intra-SR Ca(2+) diffusion. We simultaneously measured
Ca(2+) sparks and Ca(2+) blinks (localized elementary [Ca(2+)](SR)
depletions) in permeabilized ventricular cardiomyocytes over a wide
range of SR Ca(2+) loads and release fluxes. Sparks terminated via
a [Ca(2+)](SR)-dependent mechanism at a fixed [Ca(2+)](SR) depletion
threshold independent of the initial [Ca(2+)](SR) and release flux.
Ca(2+) blink recovery depended mainly on intra-SR Ca(2+) diffusion
rather than SR Ca(2+) uptake. Therefore, the large variation in Ca(2+)
blink recovery rates at different release sites occurred because
of differences in the degree of release site interconnection within
the SR network. When SR release flux was greatly reduced, long-lasting
release events occurred from well-connected junctions. These junctions
could sustain release because local SR Ca(2+) release and [Ca(2+)](SR)
refilling reached a balance, preventing [Ca(2+)](SR) from depleting
to the termination threshold. Prolonged release events eventually
terminated at a steady [Ca(2+)](SR), indicative of a slower, [Ca(2+)](SR)-independent
termination mechanism. These results demonstrate that there is high
variability in local SR connectivity but that SR Ca(2+) release terminates
at a fixed [Ca(2+)](SR) termination threshold. Thus, reliable SR
Ca(2+) release termination depends on tight RyR regulation by [Ca(2+)](SR).},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Zima, Aleksey V and Picht, Eckard and Bers, Donald M and Blatter, Lothar A},
biburl = {https://www.bibsonomy.org/bibtex/23665daf6805d4b4504be66c0f6a0774a/hake},
description = {The whole bibliography file I use.},
doi = {10.1161/CIRCRESAHA.107.183236},
file = {Zima_2008_105.pdf:Zima_2008_105.pdf:PDF},
institution = {Department of Molecular Biophysics and Physiology, Rush University
Medical Center, Chicago, IL 60612, USA.},
interhash = {a5117492f11275c292efde03676ad31a},
intrahash = {3665daf6805d4b4504be66c0f6a0774a},
journal = {Circ Res},
keywords = {ATPases, Animals; Blockers, Calcium Calcium-Transporting Cardiac, Channel Channel, Diffusion; Fluorescence; Heart Kinetics; Membrane Microscopy, Myocytes, Permeability; Potentials; Rabbits; Receptor Release Reticulum Reticulum, Ryanodine Sarcoplasmic Signaling, Ventricles, drug effects/enzymology/metabolism effects/enzymology/metabolism; effects/metabolism; effects; metabolism; pharmacology;},
month = Oct,
number = 8,
pages = {e105--e115},
pdf = {Zima_2008_105.pdf},
pii = {CIRCRESAHA.107.183236},
pmid = {18787194},
timestamp = {2009-06-03T11:21:39.000+0200},
title = {Termination of cardiac Ca2+ sparks: role of intra-SR [Ca2+], release
flux, and intra-SR Ca2+ diffusion.},
url = {http://dx.doi.org/10.1161/CIRCRESAHA.107.183236},
volume = 103,
year = 2008
}