title: The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. Single neuron dynamics.
abstract: In these companion papers, we study how the interrelated dynamics of sodium and potassium affect the excitability of neurons, the occurrence of seizures, and the stability of persistent states of activity. In this first paper, we construct a mathematical model consisting of a single conductance-based neuron together with intra- and extracellular ion concentration dynamics. We formulate a reduction of this model that permits a detailed bifurcation analysis, and show that the reduced model is a reasonable approximation of the full model. We find that competition between intrinsic neuronal currents, sodium-potassium pumps, glia, and diffusion can produce very slow and large-amplitude oscillations in ion concentrations similar to what is seen physiologically in seizures. Using the reduced model, we identify the dynamical mechanisms that give rise to these phenomena. These models reveal several experimentally testable predictions. Our work emphasizes the critical role of ion concentration homeostasis in the proper functioning of neurons, and points to important fundamental processes that may underlie pathological states such as epilepsy.
authors.affiliation: Department of Physics and Astronomy, The Center for Neural Dynamics, and The Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA. jcressma@gmu.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Cressman
authors.forename: Ghanim
authors.initials: G
authors.lastname: Ullah
authors.forename: Jokubas
authors.initials: J
authors.lastname: Ziburkus
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schiff
authors.forename: Ernest
authors.initials: E
authors.lastname: Barreto
mesh_terms: D000465:Algorithms; D004058:Diffusion; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium