Modelling Sarcoplasmic Reticulum Calcium APTase and its Regulation in Cardiac Myocytes
Geoffrey
Nunns
Bioengineering Institute, University of Auckland
Model Status
This CellML model runs in PCenv, COR and OpenCell to recreate the published results. This model only describes the standalone SERCA pump, and is based on the original matlab code dy_buffering_serca. Other versions of this model couple the SERCA pump to a reduced cardiac myocyte model.
Model Structure
ABSTRACT: When developing largescale mathematical models of physiology, some reduction in complexity is necessarily required to maintain computational efficiency. A prime example of such an intricate cell is the cardiac myocyte. For the predictive power of the cardiomyocyte models, it is vital to accurately describe the calcium transport mechanisms, since they essentially link the electrical activation to contractility. The removal of calcium from the cytoplasm takes place mainly by the Na(+)/Ca(2+) exchanger, and the sarcoplasmic reticulum Ca(2+) ATPase (SERCA). In the present study, we review the properties of SERCA, its frequencydependent and betaadrenergic regulation, and the approaches of mathematical modelling that have been used to investigate its function. Furthermore, we present novel theoretical considerations that might prove useful for the elucidation of the role of SERCA in cardiac function, achieving a reduction in model complexity, but at the same time retaining the central aspects of its function. Our results indicate that to faithfully predict the physiological properties of SERCA, we should take into account the calciumbuffering effect and reversible function of the pump. This 'uncomplicated' modelling approach could be useful to other similar transport mechanisms as well.
model diagram
Schematic diagram of SERCA pump.
The original paper reference is cited below:
Modelling Sarcoplasmic Reticulum Calcium APTase and its Regulation in Cardiac Myocytes, Jussi T. Koivumaki, Jouni Takalo, Topi Korhonen, Pasi Tavi, Matti Weckstrom, 2009, Phil. Trans. R. Soc. A, volume 367, 21812202. PubMed ID: 19414452
$\mathrm{EC\_50\_fwd}=(\mathrm{Kmf\_PLBKO}+\mathrm{Kmf\_PLB}\mathrm{PSR})(1+0.27\mathrm{CaMKII\_reg})\mathrm{EC\_50\_rev}=\mathrm{Kmr\_PLBKO}\mathrm{Kmr\_PLB}\mathrm{PSR}$
$\mathrm{br\_cyt\_serca}=1000\mathrm{br\_serca\_sr}\mathrm{k\_cyt\_serca}=\mathrm{br\_cyt\_serca}(1+0.7\mathrm{CaMKII\_reg})\mathrm{k\_serca\_cyt}=\mathrm{EC\_50\_fwd}^{2}\mathrm{br\_cyt\_serca}\mathrm{k\_serca\_sr}=\mathrm{br\_serca\_sr}(1+0.7\mathrm{CaMKII\_reg})\mathrm{k\_sr\_serca}=\frac{\mathrm{br\_serca\_sr}}{\mathrm{EC\_50\_rev}^{2}}$
$\mathrm{J\_cyt\_serca}=\mathrm{k\_cyt\_serca}\mathrm{Ca\_cyt}^{2}(\mathrm{SERCA\_TOT}\mathrm{Ca\_serca})\mathrm{k\_serca\_cyt}\mathrm{Ca\_serca}\mathrm{J\_serca\_sr}=\mathrm{k\_serca\_sr}\mathrm{Ca\_serca}\mathrm{k\_sr\_serca}\mathrm{Ca\_NSR}^{2}(\mathrm{SERCA\_TOT}\mathrm{Ca\_serca})$
$\frac{d \mathrm{Ca\_serca}}{d \mathrm{time}}=\mathrm{J\_cyt\_serca}\mathrm{J\_serca\_sr}$





Nunns
Geoffrey
Rogan

gnunns1@jhu.edu

The University of Auckland
Auckland Bioengineering Institute


20091006




The Koivumaki et al. 2009 model of SERCA pump dynamics and regulation in cardiac myocytes


This is the CellML description of Koivumaki et al.'s mathematical model of SERCA pump dynamics and regulation in cardiac myocyte


Geoffrey Nunns
Human
cardiac myocyte



keyword


electrophysiology and signal transduction
cardiac

19414452






Koivumaki
Jussi
T



Takalo
Jouni



Korhonen
Topi



Tavi
Pasi



Weckstrom
Matti

Modelling Sarcoplasmic Reticulum Calcium APTase and its Regulation in Cardiac Myocytes

20090304

Phil. Trans. R. Soc. A
367
2181
2202