Bond-graph version PMCA parameterised for uterine smc
About this model
The plasma membrane Ca2+ ATPase pump (PMCA) as parameterised in the Means, 2023 uterine smooth muscle cell model (uSMC).
| Original Publication: | |
|---|---|
| Means SA, Roesler MW, Garrett AS, Cheng L, Clark AR (2023) Steady-state approximations for Hodgkin-Huxley cell models: Reduction of order for uterine smooth muscle cell model. PLoS Comput Biol 19(8): e1011359' | |
| DOI: | https://doi.org/10.1371/journal.pcbi.1011359 |
| Secondary Publication: | |
| Tong W-C, Choi CY, Karche S, Holden AV, Zhang H, et al. (2011) A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle. PLoS ONE 6(4): e18685 | |
| DOI: | https://doi.org/10.1371/journal.pone.0018685 |
| Secondary Publication: | |
| Erin R. Higgins, Pranay Goel, Jose L. Puglisi, Donald M. Bers, Mark Cannell, James Sneyd, Modelling calcium microdomains using homogenisation, Journal of Theoretical Biology, Volume 247, Issue 4, 2007, Pages 623-644 | |
| DOI: | https://doi.org/10.1016/j.jtbi.2007.03.019 |
Model derivation
This is but one of the ion transporter sub-models of the Means, 2023 uSMC model. We converted a 6-state SERCA model from Higgins, 2006 into a 6-state PMCA model (see schematic).
Modifications were necessary to the underlying original PMCA model from Tong, 2011. Originally the model was a Hille function with an exponent of 2 indicating a stoichiometry of 2 Ca2+ per cycle, yet evidence indicates stoichiometry in the range of 1.3-1.7 (Tong, 2011). Fits between the Tong, 2011 Hille and the 6-state model show poor correspondence between them (see plot). We thus modified the Hille coefficient to '1.5' and the 6-state model stoichiometry to '1.5' as well with improved fit as shown.
Running the model
CellML implementation is provided in the file Higgins_SERCA_to_PMCA_wVm_v1.cellml and executable with the simulation environment OpenCOR. Tests reproducing the analytical steady-state as derived for the 6-state model are provided in the CellML file. Running the simulation should reproduce the ratio of intracellular to extracellular Ca2+ in the variable 'q_Ca_ratio_analytic' with the numerical solution in variable 'q_Ca_ratio.' Note, simulation time may be quit4e long out to 60,000 seconds or more.