title: Modeling the effects of extracellular potassium on bursting properties in pre-Bötzinger complex neurons.
abstract: There are many types of neurons that intrinsically generate rhythmic bursting activity, even when isolated, and these neurons underlie several specific motor behaviors. Rhythmic neurons that drive the inspiratory phase of respiration are located in the medullary pre-Bötzinger Complex (pre-BötC). However, it is not known if their rhythmic bursting is the result of intrinsic mechanisms or synaptic interactions. In many cases, for bursting to occur, the excitability of these neurons needs to be elevated. This excitation is provided in vitro (e.g. in slices), by increasing extracellular potassium concentration (K out) well beyond physiologic levels. Elevated K out shifts the reversal potentials for all potassium currents including the potassium component of leakage to higher values. However, how an increase in K out , and the resultant changes in potassium currents, induce bursting activity, have yet to be established. Moreover, it is not known if the endogenous bursting induced in vitro is representative of neural behavior in vivo. Our modeling study examines the interplay between K out, excitability, and selected currents, as they relate to endogenous rhythmic bursting. Starting with a Hodgkin-Huxley formalization of a pre-BötC neuron, a potassium ion component was incorporated into the leakage current, and model behaviors were investigated at varying concentrations of K out. Our simulations show that endogenous bursting activity, evoked in vitro by elevation of K out , is the result of a specific relationship between the leakage and voltage-dependent, delayed rectifier potassium currents, which may not be observed at physiological levels of extracellular potassium.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Room 274, 2900 W. Queen Ln., Philadelphia, PA, 19129, USA. bjb87@drexel.edu.
authors.forename: Bartholomew J
authors.identifier: http://orcid.org/0000-0003-0727-3928
authors.initials: BJ
authors.lastname: Bacak
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Segaran
authors.affiliation: Department of Mathematics & Statistics, Georgia State University, Atlanta, GA, USA.
authors.forename: Yaroslav I
authors.initials: YI
authors.lastname: Molkov
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D008526:Medulla Oblongata / Q000166:cytology*; D008959:Models, Neurological; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011188:Potassium
keywords: Computational modeling; Neuron bursting; Potassium channels; Pre-Bötzinger Complex