%0 Journal Article %1 Snyd_2000_94 %A Snyder, S. M. %A Palmer, B. M. %A Moore, R. L. %D 2000 %J Biophys. J. %K 11203466 ATPase, Animals, Calcium Calcium, Cardiovascular, Cell Channels, Compartmentation, Computer Contraction, Cytosol, Gov't, Ion Models, Muscle Myocardium, P.H.S., Predictive Rats, Research Reticulum, Sarcolemma, Sarcoplasmic Simulation, Support, Tests, Transport, U.S. Value of {C}a$^{2+}$-Transporting %N 1 %P 94-115 %T A mathematical model of cardiocyte Ca$^2+$ dynamics with a novel representation of sarcoplasmic reticular Ca$^2+$ control. %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10866940&query_hl=14 %V 79 %X Cardiac contraction and relaxation dynamics result from a set of simultaneously interacting Ca$^2+$ regulatory mechanisms. In this study, cardiocyte Ca$^2+$ dynamics were modeled using a set of six differential equations that were based on theories, equations, and parameters described in previous studies. Among the unique features of the model was the inclusion of bidirectional modulatory interplay between the sarcoplasmic reticular Ca$^2+$ release channel (SRRC) and calsequestrin (CSQ) in the SR lumen, where CSQ acted as a dynamic rather than simple Ca$^2+$ buffer, and acted as a Ca$^2+$ sensor in the SR lumen as well. The inclusion of this control mechanism was central in overcoming a number of assumptions that would otherwise have to be made about SRRC kinetics, SR Ca$^2+$ release rates, and SR Ca$^2+$ release termination when the SR lumen is assumed to act as a simple, buffered Ca$^2+$ sink. The model was sufficient to reproduce a graded Ca$^2+$-induced Ca$^2+$ release (CICR) response, CICR with high gain, and a system with reasonable stability. As constructed, the model successfully replicated the results of several previously published experiments that dealt with the Ca$^2+$ dependence of the SRRC (, J. Gen. Physiol. 85:247-289), the refractoriness of the SRRC (, Am. J. Physiol. 270:C148-C159), the SR Ca$^2+$ load dependence of SR Ca$^2+$ release (, Am. J. Physiol. 268:C1313-C1329;, J. Biol. Chem. 267:20850-20856), SR Ca$^2+$ leak (, J. Physiol. (Lond.). 474:463-471;, Biophys. J. 68:2015-2022), SR Ca$^2+$ load regulation by leak and uptake (, J. Gen. Physiol. 111:491-504), the effect of Ca$^2+$ trigger duration on SR Ca$^2+$ release (, Am. J. Physiol. 258:C944-C954), the apparent relationship that exists between sarcoplasmic and sarcoplasmic reticular calcium concentrations (, Biophys. J. 73:1524-1531), and a variety of contraction frequency-dependent alterations in sarcoplasmic Ca$^2+$ dynamics that are normally observed in the laboratory, including rest potentiation, a negative frequency-Ca$^2+$ relationship, and extrasystolic potentiation. Furthermore, under the condition of a simulated Ca$^2+$ overload, an alternans-like state was produced. In summary, the current model of cardiocyte Ca$^2+$ dynamics provides an integrated theoretical framework of fundamental cellular Ca$^2+$ regulatory processes that is sufficient to predict a broad array of observable experimental outcomes.

@article{Snyd_2000_94, abstract = {Cardiac contraction and relaxation dynamics result from a set of simultaneously interacting {C}a$^{2+}$ regulatory mechanisms. In this study, cardiocyte {C}a$^{2+}$ dynamics were modeled using a set of six differential equations that were based on theories, equations, and parameters described in previous studies. Among the unique features of the model was the inclusion of bidirectional modulatory interplay between the sarcoplasmic reticular {C}a$^{2+}$ release channel (SRRC) and calsequestrin (CSQ) in the SR lumen, where CSQ acted as a dynamic rather than simple {C}a$^{2+}$ buffer, and acted as a {C}a$^{2+}$ sensor in the SR lumen as well. The inclusion of this control mechanism was central in overcoming a number of assumptions that would otherwise have to be made about SRRC kinetics, SR {C}a$^{2+}$ release rates, and SR {C}a$^{2+}$ release termination when the SR lumen is assumed to act as a simple, buffered {C}a$^{2+}$ sink. The model was sufficient to reproduce a graded {C}a$^{2+}$-induced {C}a$^{2+}$ release (CICR) response, CICR with high gain, and a system with reasonable stability. As constructed, the model successfully replicated the results of several previously published experiments that dealt with the {C}a$^{2+}$ dependence of the SRRC (, J. Gen. Physiol. 85:247-289), the refractoriness of the SRRC (, Am. J. Physiol. 270:C148-C159), the SR {C}a$^{2+}$ load dependence of SR {C}a$^{2+}$ release (, Am. J. Physiol. 268:C1313-C1329;, J. Biol. Chem. 267:20850-20856), SR {C}a$^{2+}$ leak (, J. Physiol. (Lond.). 474:463-471;, Biophys. J. 68:2015-2022), SR {C}a$^{2+}$ load regulation by leak and uptake (, J. Gen. Physiol. 111:491-504), the effect of {C}a$^{2+}$ trigger duration on SR {C}a$^{2+}$ release (, Am. J. Physiol. 258:C944-C954), the apparent relationship that exists between sarcoplasmic and sarcoplasmic reticular calcium concentrations (, Biophys. J. 73:1524-1531), and a variety of contraction frequency-dependent alterations in sarcoplasmic [{C}a$^{2+}$] dynamics that are normally observed in the laboratory, including rest potentiation, a negative frequency-[{C}a$^{2+}$] relationship, and extrasystolic potentiation. Furthermore, under the condition of a simulated {C}a$^{2+}$ overload, an alternans-like state was produced. In summary, the current model of cardiocyte {C}a$^{2+}$ dynamics provides an integrated theoretical framework of fundamental cellular {C}a$^{2+}$ regulatory processes that is sufficient to predict a broad array of observable experimental outcomes.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Snyder, S. M. and Palmer, B. M. and Moore, R. L.}, biburl = {https://www.bibsonomy.org/bibtex/23808bcb960f31763ac44c94511a479e3/hake}, description = {The whole bibliography file I use.}, file = {Snyd_2000_94.pdf:Snyd_2000_94.pdf:PDF}, interhash = {344fc55bce66d9126e34fe27f35433a4}, intrahash = {3808bcb960f31763ac44c94511a479e3}, journal = {Biophys. J.}, key = 49, keywords = {11203466 ATPase, Animals, Calcium Calcium, Cardiovascular, Cell Channels, Compartmentation, Computer Contraction, Cytosol, Gov't, Ion Models, Muscle Myocardium, P.H.S., Predictive Rats, Research Reticulum, Sarcolemma, Sarcoplasmic Simulation, Support, Tests, Transport, U.S. Value of {C}a$^{2+}$-Transporting}, month = Jul, number = 1, pages = {94-115}, timestamp = {2009-06-03T11:21:31.000+0200}, title = {A mathematical model of cardiocyte {C}a$^{2+}$ dynamics with a novel representation of sarcoplasmic reticular {C}a$^{2+}$ control.}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10866940&query_hl=14}, volume = 79, year = 2000 }