title: Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium.
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.
authors.affiliation: MOAC Doctoral Training Centre, University of Warwick, Coventry CV4 7AL, UK. r.e.sheldon@warwick.ac.uk
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Sheldon
authors.forename: Marc
authors.initials: M
authors.lastname: Baghdadi
authors.forename: Conor
authors.initials: C
authors.lastname: McCloskey
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blanks
authors.forename: Anatoly
authors.initials: A
authors.lastname: Shmygol
authors.forename: Hugo A
authors.initials: HA
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D055724:Electrophysiological Phenomena / Q000502:physiology*; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D009215:Myometrium / Q000166:cytology / Q000502:physiology; D011247:Pregnancy / Q000502:physiology*
keywords: Fitzhugh–Nagumo; gap junction; modelling; myometrium; parturition; uterus