%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 }