A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle

A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle

Model Status

This CellML model is based on a translation of the original C code. The equations are validated using OpenCell and all units are consistent. The model can be run in both OpenCell (version 0.8) and OpenCOR (version 0.4) environments using any of the integration methods. To recreate the published results, for example figure 12 from the original paper, apply a suitable stimulating current and integrate the model for a total 10 sec with a time step of 0.02 ms.

Model Structure

ABSTRACT: Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine Ca2+ -dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for thirteen ionic currents of USMCs: Ca2+ currents (L- and T-type), Na+ current, and hyperpolarization-activated current, three voltage-gated K+ currents, Ca2+ -activated K+ current,Ca2+ -activated Cl- current, non-specific cation current, Na+ -Ca2+ exchanger, Na+ -K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modelled in relation to the time constant of changing [Ca2+ ]i . This integrated model is validated by its reconstruction of the different action potential configurations of USMCs (spikes,plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol, and of simultaneous experimental recordings of spontaneous AP, [Ca2+ ]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical excitation-contraction coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.

The original paper reference is cited below:

A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle. Wing-Chiu Tong, Cecilia Y. Choi, Sanjay Kharche, Arun V. Holden, Henggui Zhang and Michael J. Taggart, 2011, PLoS One, 6(4), e18685. PubMed ID: 21559514

A schematic diagram of the Tong et. al. 2011 uterine smooth muscle cell model.