Abstract
Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials – from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes – that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes.
Highlights
Disorders in uterine excitation or contractility can lead to a range of complications for the mother and child, including preterm birth, ineffective and long labour, and post-partum haemorrhage
With the validated cell model, we theoretically investigated the role of changing Na+ and Ca2+ ion channel current density in modulating cellular action potentials, the intracellular Ca2+ handling and the genesis of active force, exploring effects of possible ion channel remodelling during the gestational period on uterine cellular electrical and mechanical activities
The simulated bursting action potentials, stair-case increase of the intracellular Ca2+ transient and the resultant cellular active force matched to examples of experimental data as shown by the insets in Fig. 2, which show the typical morphology of membrane potentials, calcium transients and force profiles in uterine cells from late-pregnant rat
Summary
Disorders in uterine excitation or contractility can lead to a range of complications for the mother and child, including preterm birth, ineffective and long labour, and post-partum haemorrhage. We demonstrated the model’s capability in reproducing the effects of some drugs and hormones on cellular electrical and mechanical activities All of these simulation results qualitatively and quantitatively match to experimental data, validating the cell model development. With the validated cell model, we theoretically investigated the role of changing Na+ and Ca2+ ion channel current density in modulating cellular action potentials, the intracellular Ca2+ handling and the genesis of active force, exploring effects of possible ion channel remodelling during the gestational period on uterine cellular electrical and mechanical activities.
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