title: Diffusion of extracellular K+ can synchronize bursting oscillations in a model islet of Langerhans.
abstract: Electrical bursting oscillations of mammalian pancreatic beta-cells are synchronous among cells within an islet. While electrical coupling among cells via gap junctions has been demonstrated, its extent and topology are unclear. The beta-cells also share an extracellular compartment in which oscillations of K+ concentration have been measured (Perez-Armendariz and Atwater, 1985). These oscillations (1-2 mM) are synchronous with the burst pattern, and apparently are caused by the oscillating voltage-dependent membrane currents: Extracellular K+ concentration (Ke) rises during the depolarized active (spiking) phase and falls during the hyperpolarized silent phase. Because raising Ke depolarizes the cell membrane by increasing the potassium reversal potential (VK), any cell in the active phase should recruit nonspiking cells into the active phase. The opposite is predicted for the silent phase. This positive feedback system might couple the cells' electrical activity and synchronize bursting. We have explored this possibility using a theoretical model for bursting of beta-cells (Sherman et al., 1988) and K+ diffusion in the extracellular space of an islet. Computer simulations demonstrate that the bursts synchronize very quickly (within one burst) without gap junctional coupling among the cells. The shape and amplitude of computed Ke oscillations resemble those seen in experiments for certain parameter ranges. The model cells synchronize with exterior cells leading, though incorporating heterogeneous cell properties can allow interior cells to lead. The model islet can also be forced to oscillate at both faster and slower frequencies using periodic pulses of higher K+ in the medium surrounding the islet. Phase plane analysis was used to understand the synchronization mechanism. The results of our model suggest that diffusion of extracellular K+ may contribute to coupling and synchronization of electrical oscillations in beta-cells within an islet.
authors.affiliation: Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: C L
authors.initials: CL
authors.lastname: Stokes
authors.forename: J
authors.initials: J
authors.lastname: Rinzel
mesh_terms: D000818:Animals; D005110:Extracellular Space / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D007700:Kinetics; D008322:Mammals; D008433:Mathematics; D008954:Models, Biological; D009991:Oscillometry; D011188:Potassium / Q000378:metabolism*
chemical_list: D011188:Potassium