%0 Journal Article %1 Jafr_1998_1149 %A Jafri, M. S. %A Rice, J. J. %A Winslow, R. L. %D 1998 %J Biophys. J. %K 9512016 Action Animals, Calcium Calcium, Cardiovascular, Channel Channel, Channels, Chemical, Contraction, Electric Factors, Gating, Gov't, Guinea Heart In Ion Kinetics, L-Type, Models, Myocardial Myocardium, Non-P.H.S., Non-U.S. Pigs, Potentials, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Stimulation, Support, Time U.S. Ventricles, Vitro, %N 3 %P 1149-68 %T Cardiac Ca$^2+$ dynamics: the roles of ryanodine receptor adaptation and sarcoplasmic reticulum load. %U http://www.biophysj.org/cgi/content/full/74/3/1149 %V 74 %X We construct a detailed mathematical model for Ca$^2+$ regulation in the ventricular myocyte that includes novel descriptions of subcellular mechanisms based on recent experimental findings: 1) the Keizer-Levine model for the ryanodine receptor (RyR), which displays adaptation at elevated Ca$^2+$; 2) a model for the L-type Ca$^2+$ channel that inactivates by mode switching; and 3) a restricted subspace into which the RyRs and L-type Ca$^2+$ channels empty and interact via Ca$^2+$. We add membrane currents from the Luo-Rudy Phase II ventricular cell model to our description of Ca$^2+$ handling to formulate a new model for ventricular action potentials and Ca$^2+$ regulation. The model can simulate Ca$^2+$ transients during an action potential similar to those seen experimentally. The subspace Ca$^2+$ rises more rapidly and reaches a higher level (10-30 microM) than the bulk myoplasmic Ca$^2+$ (peak Ca$^2+$i approximately 1 microM). Termination of sarcoplasmic reticulum (SR) Ca$^2+$ release is predominately due to emptying of the SR, but is influenced by RyR adaptation. Because force generation is roughly proportional to peak myoplasmic Ca$^2+$, we use Ca$^2+$i in the model to explore the effects of pacing rate on force generation. The model reproduces transitions seen in force generation due to changes in pacing that cannot be simulated by previous models. Simulation of such complex phenomena requires an interplay of both RyR adaptation and the degree of SR Ca$^2+$ loading. This model, therefore, shows improved behavior over existing models that lack detailed descriptions of subcellular Ca$^2+$ regulatory mechanisms.

@article{Jafr_1998_1149, abstract = {We construct a detailed mathematical model for {C}a$^{2+}$ regulation in the ventricular myocyte that includes novel descriptions of subcellular mechanisms based on recent experimental findings: 1) the Keizer-Levine model for the ryanodine receptor (RyR), which displays adaptation at elevated {C}a$^{2+}$; 2) a model for the L-type {C}a$^{2+}$ channel that inactivates by mode switching; and 3) a restricted subspace into which the RyRs and L-type {C}a$^{2+}$ channels empty and interact via {C}a$^{2+}$. We add membrane currents from the Luo-Rudy Phase II ventricular cell model to our description of {C}a$^{2+}$ handling to formulate a new model for ventricular action potentials and {C}a$^{2+}$ regulation. The model can simulate {C}a$^{2+}$ transients during an action potential similar to those seen experimentally. The subspace [{C}a$^{2+}$] rises more rapidly and reaches a higher level (10-30 microM) than the bulk myoplasmic {C}a$^{2+}$ (peak [{C}a$^{2+}$]i approximately 1 microM). Termination of sarcoplasmic reticulum (SR) {C}a$^{2+}$ release is predominately due to emptying of the SR, but is influenced by RyR adaptation. Because force generation is roughly proportional to peak myoplasmic {C}a$^{2+}$, we use [{C}a$^{2+}$]i in the model to explore the effects of pacing rate on force generation. The model reproduces transitions seen in force generation due to changes in pacing that cannot be simulated by previous models. Simulation of such complex phenomena requires an interplay of both RyR adaptation and the degree of SR {C}a$^{2+}$ loading. This model, therefore, shows improved behavior over existing models that lack detailed descriptions of subcellular {C}a$^{2+}$ regulatory mechanisms.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Jafri, M. S. and Rice, J. J. and Winslow, R. L.}, biburl = {https://www.bibsonomy.org/bibtex/201c14328413c27da5af35e2901c3642b/hake}, description = {The whole bibliography file I use.}, file = {Jafr_1998_1149.pdf:Jafr_1998_1149.pdf:PDF}, interhash = {939913ec20f0432002f06f0aafcd4d7a}, intrahash = {01c14328413c27da5af35e2901c3642b}, journal = {Biophys. J.}, key = 3, keywords = {9512016 Action Animals, Calcium Calcium, Cardiovascular, Channel Channel, Channels, Chemical, Contraction, Electric Factors, Gating, Gov't, Guinea Heart In Ion Kinetics, L-Type, Models, Myocardial Myocardium, Non-P.H.S., Non-U.S. Pigs, Potentials, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Stimulation, Support, Time U.S. Ventricles, Vitro,}, month = Mar, number = 3, pages = {1149-68}, timestamp = {2009-06-03T11:21:16.000+0200}, title = {Cardiac {C}a$^{2+}$ dynamics: the roles of ryanodine receptor adaptation and sarcoplasmic reticulum load.}, url = {http://www.biophysj.org/cgi/content/full/74/3/1149}, volume = 74, year = 1998 }