A model of the functional release unit (FRU) in rat cardiac muscle
consisting of one dihydropyridine receptor (DHPR) and eight ryanodine
receptor (RyR) channels, and the volume surrounding them, is formulated.
It is assumed that no spatial Ca$^2+$ gradients exist in this
volume, and that each FRU acts independently. The model is amenable
to systematic parameter studies in which FRU dynamics are simulated
at the channel level using Monte Carlo methods with Ca$^2+$ concentrations
simulated by numerical integration of a coupled system of differential
equations. Using stochastic methods, Ca$^2+$-induced Ca$^2+$
release (CICR) shows both high gain and graded Ca$^2+$ release
that is robust when parameters are varied. For a single DHPR opening,
the resulting RyR Ca$^2+$ release flux is insensitive to the
DHPR open duration, and is determined principally by local sarcoplasmic
reticulum (SR) Ca$^2+$ load, consistent with experimental data
on Ca$^2+$ sparks. In addition, single RyR openings are effective
in triggering Ca$^2+$ release from adjacent RyRs only when open
duration is long and SR Ca$^2+$ load is high. This indicates
relatively low coupling between RyRs, and suggests a mechanism that
limits the regenerative spread of RyR openings. The results also
suggest that adaptation plays an important modulatory role in shaping
Ca$^2+$ release duration and magnitude, but is not solely responsible
for terminating Ca$^2+$ release. Results obtained with the stochastic
model suggest that high gain and gradedness can occur by the recruitment
of independent FRUs without requiring spatial Ca$^2+$ gradients
within a functional unit or cross-coupling between adjacent functional
units.
%0 Journal Article
%1 Rice_1999_1871
%A Rice, J. J.
%A Jafri, M. S.
%A Winslow, R. L.
%D 1999
%J Biophys. J.
%K 10512809 Action Animals, Biological, Calcium Calcium, Car, Carlo Channel Channel, Channels, Contraction, Electric Factors, Gating, Guinea Heart In Ion Kinetics, L-Type, Method, Models, Monte Myocardial Myocardium, Patch-Clamp Pigs, Potentials, Rats, Receptor Release Reticulum, Ryanodine Sarcoplasmic Stimulation, Techniques, Time Ventricles, Vitro, diovascular,
%N 4
%P 1871--1884
%T Modeling gain and gradedness of Ca$^2+$ release in the functional
unit of the cardiac diadic space.
%U http://www.biophysj.org/cgi/content/full/77/4/1871
%V 77
%X A model of the functional release unit (FRU) in rat cardiac muscle
consisting of one dihydropyridine receptor (DHPR) and eight ryanodine
receptor (RyR) channels, and the volume surrounding them, is formulated.
It is assumed that no spatial Ca$^2+$ gradients exist in this
volume, and that each FRU acts independently. The model is amenable
to systematic parameter studies in which FRU dynamics are simulated
at the channel level using Monte Carlo methods with Ca$^2+$ concentrations
simulated by numerical integration of a coupled system of differential
equations. Using stochastic methods, Ca$^2+$-induced Ca$^2+$
release (CICR) shows both high gain and graded Ca$^2+$ release
that is robust when parameters are varied. For a single DHPR opening,
the resulting RyR Ca$^2+$ release flux is insensitive to the
DHPR open duration, and is determined principally by local sarcoplasmic
reticulum (SR) Ca$^2+$ load, consistent with experimental data
on Ca$^2+$ sparks. In addition, single RyR openings are effective
in triggering Ca$^2+$ release from adjacent RyRs only when open
duration is long and SR Ca$^2+$ load is high. This indicates
relatively low coupling between RyRs, and suggests a mechanism that
limits the regenerative spread of RyR openings. The results also
suggest that adaptation plays an important modulatory role in shaping
Ca$^2+$ release duration and magnitude, but is not solely responsible
for terminating Ca$^2+$ release. Results obtained with the stochastic
model suggest that high gain and gradedness can occur by the recruitment
of independent FRUs without requiring spatial Ca$^2+$ gradients
within a functional unit or cross-coupling between adjacent functional
units.
@article{Rice_1999_1871,
abstract = {A model of the functional release unit ({FRU}) in rat cardiac muscle
consisting of one dihydropyridine receptor (DHPR) and eight ryanodine
receptor (RyR) channels, and the volume surrounding them, is formulated.
It is assumed that no spatial [{C}a$^{2+}$] gradients exist in this
volume, and that each {FRU} acts independently. The model is amenable
to systematic parameter studies in which {FRU} dynamics are simulated
at the channel level using Monte Carlo methods with {C}a$^{2+}$ concentrations
simulated by numerical integration of a coupled system of differential
equations. Using stochastic methods, {C}a$^{2+}$-induced {C}a$^{2+}$
release (CICR) shows both high gain and graded {C}a$^{2+}$ release
that is robust when parameters are varied. For a single DHPR opening,
the resulting RyR {C}a$^{2+}$ release flux is insensitive to the
DHPR open duration, and is determined principally by local sarcoplasmic
reticulum (SR) {C}a$^{2+}$ load, consistent with experimental data
on {C}a$^{2+}$ sparks. In addition, single RyR openings are effective
in triggering {C}a$^{2+}$ release from adjacent RyRs only when open
duration is long and SR {C}a$^{2+}$ load is high. This indicates
relatively low coupling between RyRs, and suggests a mechanism that
limits the regenerative spread of RyR openings. The results also
suggest that adaptation plays an important modulatory role in shaping
{C}a$^{2+}$ release duration and magnitude, but is not solely responsible
for terminating {C}a$^{2+}$ release. Results obtained with the stochastic
model suggest that high gain and gradedness can occur by the recruitment
of independent {FRU}s without requiring spatial [{C}a$^{2+}$] gradients
within a functional unit or cross-coupling between adjacent functional
units.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Rice, J. J. and Jafri, M. S. and Winslow, R. L.},
biburl = {https://www.bibsonomy.org/bibtex/2578f5372d25beb4115708d246e523644/hake},
description = {The whole bibliography file I use.},
file = {Rice_1999_1871.pdf:Rice_1999_1871.pdf:PDF},
interhash = {6b239c888bb7ac1b9be4bd45a244e865},
intrahash = {578f5372d25beb4115708d246e523644},
journal = {Biophys. J.},
key = 152,
keywords = {10512809 Action Animals, Biological, Calcium Calcium, Car, Carlo Channel Channel, Channels, Contraction, Electric Factors, Gating, Guinea Heart In Ion Kinetics, L-Type, Method, Models, Monte Myocardial Myocardium, Patch-Clamp Pigs, Potentials, Rats, Receptor Release Reticulum, Ryanodine Sarcoplasmic Stimulation, Techniques, Time Ventricles, Vitro, diovascular,},
month = Oct,
number = 4,
pages = {1871--1884},
pmid = {10512809},
timestamp = {2009-06-03T11:21:26.000+0200},
title = {Modeling gain and gradedness of {C}a$^{2+}$ release in the functional
unit of the cardiac diadic space.},
url = {http://www.biophysj.org/cgi/content/full/77/4/1871},
volume = 77,
year = 1999
}