A Ca$^2+$ spark arises when a cluster of sarcoplasmic reticulum
(SR) channels (ryanodine receptors or RyRs) opens to release calcium
in a locally regenerative manner. Normally triggered by Ca$^2+$
influx across the sarcolemmal or transverse tubule membrane neighboring
the cluster, the Ca$^2+$ spark has been shown to be the elementary
Ca$^2+$ signaling event of excitation-contraction coupling in
heart muscle. However, the question of how the Ca$^2+$ spark
terminates remains a central, unresolved issue. Here we present a
new model, "sticky cluster," of SR Ca$^2+$ release that simulates
Ca$^2+$ spark behavior and enables robust Ca$^2+$ spark termination.
Two newly documented features of RyR behavior have been incorporated
in this otherwise simple model: "coupled gating" and an opening rate
that depends on SR lumenal Ca$^2+$. Using a Monte Carlo method,
local Ca$^2+$-induced Ca$^2+$ release from clusters containing
between 10 and 100 RyRs is modeled. After release is triggered, Ca$^2+$
flux from RyRs diffuses into the cytosol and binds to intracellular
buffers and the fluorescent Ca$^2+$ indicator fluo-3 to produce
the model Ca$^2+$ spark. Ca$^2+$ sparks generated by the
sticky cluster model resemble those observed experimentally, and
Ca$^2+$ spark duration and amplitude are largely insensitive
to the number of RyRs in a cluster. As expected from heart cell investigation,
the spontaneous Ca$^2+$ spark rate in the model increases with
elevated cytosolic or SR lumenal Ca$^2+$. Furthermore, reduction
of RyR coupling leads to prolonged model Ca$^2+$ sparks just
as treatment with FK506 lengthens Ca$^2+$ sparks in heart cells.
This new model of Ca$^2+$ spark behavior provides a "proof of
principle" test of a new hypothesis for Ca$^2+$ spark termination
and reproduces critical features of Ca$^2+$ sparks observed experimentally.
%0 Journal Article
%1 Sobi_2002_59
%A Sobie, Eric A
%A Dilly, Keith W
%A dos Santos Cruz, Jader
%A Lederer, W. Jonathan
%A Jafri, M. Saleet
%D 2002
%J Biophys. J.
%K 12080100 Agents, Animals, Biological, Calci, Calcium Calcium, Cardiac, Carlo Channel, Channels, Confocal, Congestive, Factors, Failure, Fluorescence, Gov't, Guinea Heart Immunosuppressive Kinetics, L-Type, Method, Mice, Microscopy, Models, Monte Myocardium, Myocytes, P.H.S., Pigs, Rats, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Signal Signaling, Sirolimus, Support, Tacrolimus, Temperature, Theoretical, Time Transduction, U.S. um,
%N 1
%P 59--78
%T Termination of cardiac Ca$^2+$ sparks: an investigative mathematical
model of calcium-induced calcium release.
%U http://www.biophysj.org/cgi/content/full/83/1/59
%V 83
%X A Ca$^2+$ spark arises when a cluster of sarcoplasmic reticulum
(SR) channels (ryanodine receptors or RyRs) opens to release calcium
in a locally regenerative manner. Normally triggered by Ca$^2+$
influx across the sarcolemmal or transverse tubule membrane neighboring
the cluster, the Ca$^2+$ spark has been shown to be the elementary
Ca$^2+$ signaling event of excitation-contraction coupling in
heart muscle. However, the question of how the Ca$^2+$ spark
terminates remains a central, unresolved issue. Here we present a
new model, "sticky cluster," of SR Ca$^2+$ release that simulates
Ca$^2+$ spark behavior and enables robust Ca$^2+$ spark termination.
Two newly documented features of RyR behavior have been incorporated
in this otherwise simple model: "coupled gating" and an opening rate
that depends on SR lumenal Ca$^2+$. Using a Monte Carlo method,
local Ca$^2+$-induced Ca$^2+$ release from clusters containing
between 10 and 100 RyRs is modeled. After release is triggered, Ca$^2+$
flux from RyRs diffuses into the cytosol and binds to intracellular
buffers and the fluorescent Ca$^2+$ indicator fluo-3 to produce
the model Ca$^2+$ spark. Ca$^2+$ sparks generated by the
sticky cluster model resemble those observed experimentally, and
Ca$^2+$ spark duration and amplitude are largely insensitive
to the number of RyRs in a cluster. As expected from heart cell investigation,
the spontaneous Ca$^2+$ spark rate in the model increases with
elevated cytosolic or SR lumenal Ca$^2+$. Furthermore, reduction
of RyR coupling leads to prolonged model Ca$^2+$ sparks just
as treatment with FK506 lengthens Ca$^2+$ sparks in heart cells.
This new model of Ca$^2+$ spark behavior provides a "proof of
principle" test of a new hypothesis for Ca$^2+$ spark termination
and reproduces critical features of Ca$^2+$ sparks observed experimentally.
@article{Sobi_2002_59,
abstract = {A {C}a$^{2+}$ spark arises when a cluster of sarcoplasmic reticulum
(SR) channels (ryanodine receptors or RyRs) opens to release calcium
in a locally regenerative manner. Normally triggered by {C}a$^{2+}$
influx across the sarcolemmal or transverse tubule membrane neighboring
the cluster, the {C}a$^{2+}$ spark has been shown to be the elementary
{C}a$^{2+}$ signaling event of excitation-contraction coupling in
heart muscle. However, the question of how the {C}a$^{2+}$ spark
terminates remains a central, unresolved issue. Here we present a
new model, "sticky cluster," of SR {C}a$^{2+}$ release that simulates
{C}a$^{2+}$ spark behavior and enables robust {C}a$^{2+}$ spark termination.
Two newly documented features of RyR behavior have been incorporated
in this otherwise simple model: "coupled gating" and an opening rate
that depends on SR lumenal [{C}a$^{2+}$]. Using a Monte Carlo method,
local {C}a$^{2+}$-induced {C}a$^{2+}$ release from clusters containing
between 10 and 100 RyRs is modeled. After release is triggered, {C}a$^{2+}$
flux from RyRs diffuses into the cytosol and binds to intracellular
buffers and the fluorescent {C}a$^{2+}$ indicator fluo-3 to produce
the model {C}a$^{2+}$ spark. {C}a$^{2+}$ sparks generated by the
sticky cluster model resemble those observed experimentally, and
{C}a$^{2+}$ spark duration and amplitude are largely insensitive
to the number of RyRs in a cluster. As expected from heart cell investigation,
the spontaneous {C}a$^{2+}$ spark rate in the model increases with
elevated cytosolic or SR lumenal [{C}a$^{2+}$]. Furthermore, reduction
of RyR coupling leads to prolonged model {C}a$^{2+}$ sparks just
as treatment with FK506 lengthens {C}a$^{2+}$ sparks in heart cells.
This new model of {C}a$^{2+}$ spark behavior provides a "proof of
principle" test of a new hypothesis for {C}a$^{2+}$ spark termination
and reproduces critical features of {C}a$^{2+}$ sparks observed experimentally.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Sobie, Eric A and Dilly, Keith W and dos Santos Cruz, Jader and Lederer, W. Jonathan and Jafri, M. Saleet},
biburl = {https://www.bibsonomy.org/bibtex/21cb16989ecd9baf9f136e0f154befa8f/hake},
description = {The whole bibliography file I use.},
file = {Sobi_2002_59.pdf:Sobi_2002_59.pdf:PDF},
interhash = {a8d7ee86a1de7740fd57c4cb3f3d7e75},
intrahash = {1cb16989ecd9baf9f136e0f154befa8f},
journal = {Biophys. J.},
key = 95,
keywords = {12080100 Agents, Animals, Biological, Calci, Calcium Calcium, Cardiac, Carlo Channel, Channels, Confocal, Congestive, Factors, Failure, Fluorescence, Gov't, Guinea Heart Immunosuppressive Kinetics, L-Type, Method, Mice, Microscopy, Models, Monte Myocardium, Myocytes, P.H.S., Pigs, Rats, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Signal Signaling, Sirolimus, Support, Tacrolimus, Temperature, Theoretical, Time Transduction, U.S. um,},
month = Jul,
number = 1,
pages = {59--78},
pmid = {12080100},
timestamp = {2009-06-03T11:21:31.000+0200},
title = {Termination of cardiac {C}a$^{2+}$ sparks: an investigative mathematical
model of calcium-induced calcium release.},
url = {http://www.biophysj.org/cgi/content/full/83/1/59},
volume = 83,
year = 2002
}