We have developed a model of Ca$^2+$ handling in ferret ventricular
myocytes. This model includes a novel L-type Ca$^2+$ channel,
detailed intracellular Ca$^2+$ movements, and graded Ca$^2+$-induced
Ca$^2+$ release (CICR). The model successfully reproduces data
from voltage-clamp experiments, including voltage- and time-dependent
changes in intracellular Ca$^2+$ concentration (Ca$^2+$(i)),
L-type Ca$^2+$ channel current (I(CaL)) inactivation and recovery
kinetics, and Ca$^2+$ sparks. The development of graded CICR
is critically dependent on spatial heterogeneity and the physical
arrangement of calcium channels in opposition to ryanodine-sensitive
release channels. The model contains spatially distinct subsystems
representing the subsarcolemmal regions where the junctional sarcoplasmic
reticulum (SR) abuts the T-tubular membrane and where the L-type
Ca$^2+$ channels and SR ryanodine receptors (RyRs) are localized.
There are eight different types of subsystems in our model, with
between one and eight L-type Ca$^2+$ channels distributed binomially.
This model exhibits graded CICR and provides a quantitative description
of Ca$^2+$ dynamics not requiring Monte-Carlo simulations. Activation
of RyRs and release of Ca$^2+$ from the SR depend critically
on Ca$^2+$ entry through L-type Ca$^2+$ channels. In turn,
Ca$^2+$ channel inactivation is critically dependent on the release
of stored intracellular Ca$^2+$. Inactivation of I(CaL) depends
on both transmembrane voltage and local Ca$^2+$(i) near the
channel, which results in distinctive inactivation properties. The
molecular mechanisms underlying many I(CaL) gating properties are
unclear, but Ca$^2+$(i) dynamics clearly play a fundamental
role.
%0 Journal Article
%1 Bond_2004_H1154
%A Bondarenko, Vladimir E
%A Bett, Glenna C L
%A Rasmusson, Randall L
%D 2004
%J Am. J. Physiol. Heart Circ. Physiol.
%K 14630639 Action Animals, Calcium Calcium, Cardiac, Cardiovascular, Channel Channels, Chloride Computer Conductivity, Electric Ferrets, Function, Gating, Gov't, Homeostasis, Ion L-Type, Mice, Models, Myocytes, Non-P.H.S., Non-U.S. P.H.S., Patch-Clamp Potassium Potentials, Research Reticulum, Sarcoplasmic Simulation, Sodium Support, Techniques, U.S. Ventricular Voltage-Gated,
%N 3
%P H1154--H1169
%R 10.1152/ajpheart.00168.2003
%T A model of graded calcium release and L-type Ca$^2+$ channel
inactivation in cardiac muscle.
%U http://dx.doi.org/10.1152/ajpheart.00168.2003
%V 286
%X We have developed a model of Ca$^2+$ handling in ferret ventricular
myocytes. This model includes a novel L-type Ca$^2+$ channel,
detailed intracellular Ca$^2+$ movements, and graded Ca$^2+$-induced
Ca$^2+$ release (CICR). The model successfully reproduces data
from voltage-clamp experiments, including voltage- and time-dependent
changes in intracellular Ca$^2+$ concentration (Ca$^2+$(i)),
L-type Ca$^2+$ channel current (I(CaL)) inactivation and recovery
kinetics, and Ca$^2+$ sparks. The development of graded CICR
is critically dependent on spatial heterogeneity and the physical
arrangement of calcium channels in opposition to ryanodine-sensitive
release channels. The model contains spatially distinct subsystems
representing the subsarcolemmal regions where the junctional sarcoplasmic
reticulum (SR) abuts the T-tubular membrane and where the L-type
Ca$^2+$ channels and SR ryanodine receptors (RyRs) are localized.
There are eight different types of subsystems in our model, with
between one and eight L-type Ca$^2+$ channels distributed binomially.
This model exhibits graded CICR and provides a quantitative description
of Ca$^2+$ dynamics not requiring Monte-Carlo simulations. Activation
of RyRs and release of Ca$^2+$ from the SR depend critically
on Ca$^2+$ entry through L-type Ca$^2+$ channels. In turn,
Ca$^2+$ channel inactivation is critically dependent on the release
of stored intracellular Ca$^2+$. Inactivation of I(CaL) depends
on both transmembrane voltage and local Ca$^2+$(i) near the
channel, which results in distinctive inactivation properties. The
molecular mechanisms underlying many I(CaL) gating properties are
unclear, but Ca$^2+$(i) dynamics clearly play a fundamental
role.
@article{Bond_2004_H1154,
abstract = {We have developed a model of {C}a$^{2+}$ handling in ferret ventricular
myocytes. This model includes a novel L-type {C}a$^{2+}$ channel,
detailed intracellular {C}a$^{2+}$ movements, and graded {C}a$^{2+}$-induced
{C}a$^{2+}$ release (CICR). The model successfully reproduces data
from voltage-clamp experiments, including voltage- and time-dependent
changes in intracellular {C}a$^{2+}$ concentration ([{C}a$^{2+}$](i)),
L-type {C}a$^{2+}$ channel current (I(CaL)) inactivation and recovery
kinetics, and {C}a$^{2+}$ sparks. The development of graded CICR
is critically dependent on spatial heterogeneity and the physical
arrangement of calcium channels in opposition to ryanodine-sensitive
release channels. The model contains spatially distinct subsystems
representing the subsarcolemmal regions where the junctional sarcoplasmic
reticulum (SR) abuts the T-tubular membrane and where the L-type
{C}a$^{2+}$ channels and SR ryanodine receptors (RyRs) are localized.
There are eight different types of subsystems in our model, with
between one and eight L-type {C}a$^{2+}$ channels distributed binomially.
This model exhibits graded CICR and provides a quantitative description
of {C}a$^{2+}$ dynamics not requiring Monte-Carlo simulations. Activation
of RyRs and release of {C}a$^{2+}$ from the SR depend critically
on {C}a$^{2+}$ entry through L-type {C}a$^{2+}$ channels. In turn,
{C}a$^{2+}$ channel inactivation is critically dependent on the release
of stored intracellular {C}a$^{2+}$. Inactivation of I(CaL) depends
on both transmembrane voltage and local [{C}a$^{2+}$](i) near the
channel, which results in distinctive inactivation properties. The
molecular mechanisms underlying many I(CaL) gating properties are
unclear, but [{C}a$^{2+}$](i) dynamics clearly play a fundamental
role.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Bondarenko, Vladimir E and Bett, Glenna C L and Rasmusson, Randall L},
biburl = {https://www.bibsonomy.org/bibtex/21c1b0fc37444aac819363fd937d44947/hake},
description = {The whole bibliography file I use.},
doi = {10.1152/ajpheart.00168.2003},
file = {Bond_2004_H1154.pdf:Bond_2004_H1154.pdf:PDF},
interhash = {cf0bff02afcb9f6a1cacb3921715ce39},
intrahash = {1c1b0fc37444aac819363fd937d44947},
journal = {Am. J. Physiol. Heart Circ. Physiol.},
key = 61,
keywords = {14630639 Action Animals, Calcium Calcium, Cardiac, Cardiovascular, Channel Channels, Chloride Computer Conductivity, Electric Ferrets, Function, Gating, Gov't, Homeostasis, Ion L-Type, Mice, Models, Myocytes, Non-P.H.S., Non-U.S. P.H.S., Patch-Clamp Potassium Potentials, Research Reticulum, Sarcoplasmic Simulation, Sodium Support, Techniques, U.S. Ventricular Voltage-Gated,},
month = Mar,
number = 3,
pages = {H1154--H1169},
pdf = {Bond_2004_H1154.pdf},
pii = {00168.2003},
pmid = {14630639},
timestamp = {2009-06-03T11:21:06.000+0200},
title = {A model of graded calcium release and L-type {C}a$^{2+}$ channel
inactivation in cardiac muscle.},
url = {http://dx.doi.org/10.1152/ajpheart.00168.2003},
volume = 286,
year = 2004
}