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Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium
Authors:Rachel E Sheldon  Marc Baghdadi  Conor McCloskey  Andrew M Blanks  Anatoly Shmygol  Hugo A van den Berg
Affiliation:1.MOAC Doctoral Training Centre, University of Warwick, Coventry CV4 7AL, UK;2.Systems Biology, University of Warwick, Coventry CV4 7AL, UK;3.Division of Reproductive Health, Warwick Medical School, Coventry CV2 2DX, UK
Abstract:The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability.
Keywords:uterus  myometrium  gap junction  modelling  Fitzhugh–  Nagumo  parturition
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