Dataset Information

DeVries2000_PancreaticBetaCells_InsulinSecretion

ABSTRACT: This a model from the article: Channel sharing in pancreatic beta -cells revisited: enhancement of emergent bursting by noise. De Vries G, Sherman A. J Theor Biol2000 Dec 21;207(4):513-30 11093836, Abstract: Secretion of insulin by electrically coupled populations of pancreatic beta -cells is governed by bursting electrical activity. Isolated beta -cells, however, exhibit atypical bursting or continuous spike activity. We study bursting as an emergent property of the population, focussing on interactions among the subclass of spiking cells. These are modelled by equipping the fast subsystem with a saddle-node-loop bifurcation, which makes it monostable. Such cells can only spike tonically or remain silent when isolated, but can be induced to burst with weak diffusive coupling. With stronger coupling, the cells revert to tonic spiking. We demonstrate that the addition of noise dramatically increases, via a phenomenon like stochastic resonance, the coupling range over which bursting is seen. Copyright 2000 Academic Press. This model was taken from the CellML repository and automatically converted to SBML. The original model was: De Vries G, Sherman A. (2000) - version01 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

DISEASE(S): Diabetes Mellitus

SUBMITTER: Vijayalakshmi Chelliah

PROVIDER: BIOMD0000000371 | BioModels | 2011-09-28

REPOSITORIES: BioModels

ACCESS DATA

Publications

Channel sharing in pancreatic beta -cells revisited: enhancement of emergent bursting by noise.

De Vries G G Sherman A A

Journal of theoretical biology 20001201 4

Secretion of insulin by electrically coupled populations of pancreatic beta -cells is governed by bursting electrical activity. Isolated beta -cells, however, exhibit atypical bursting or continuous spike activity. We study bursting as an emergent property of the population, focussing on interactions among the subclass of spiking cells. These are modelled by equipping the fast subsystem with a saddle-node-loop bifurcation, which makes it monostable. Such cells can only spike tonically or remain ...[more]

PMID: 11093836

Publication: 1/2

Similar Datasets

Project description:This a model from the article: The phantom burster model for pancreatic beta-cells. Bertram R, Previte J, Sherman A, Kinard TA, Satin LS. Biophys J2000 Dec;79(6):2880-92 11106596, Abstract: Pancreatic beta-cells exhibit bursting oscillations with a wide range of periods. Whereas periods in isolated cells are generally either a few seconds or a few minutes, in intact islets of Langerhans they are intermediate (10-60 s). We develop a mathematical model for beta-cell electrical activity capable of generating this wide range of bursting oscillations. Unlike previous models, bursting is driven by the interaction of two slow processes, one with a relatively small time constant (1-5 s) and the other with a much larger time constant (1-2 min). Bursting on the intermediate time scale is generated without need for a slow process having an intermediate time constant, hence phantom bursting. The model suggests that isolated cells exhibiting a fast pattern may nonetheless possess slower processes that can be brought out by injecting suitable exogenous currents. Guided by this, we devise an experimental protocol using the dynamic clamp technique that reliably elicits islet-like, medium period oscillations from isolated cells. Finally, we show that strong electrical coupling between a fast burster and a slow burster can produce synchronized medium bursting, suggesting that islets may be composed of cells that are intrinsically either fast or slow, with few or none that are intrinsically medium. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Bertram R, Previte J, Sherman A, Kinard TA, Satin LS. (2000) - version02 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:Dravet syndrome is a developmental and epileptic encephalopathy characterized by seizures, behavioral abnormalities, developmental deficits, and elevated risk of sudden unexpected death in epilepsy (SUDEP). Most patient cases are caused by de novo loss-of-function mutations in the gene SCN1A, causing a haploinsufficiency of the alpha subunit of the voltage-gated sodium channel NaV1.1. Within the brain, NaV1.1 is primarily localized to the axons of inhibitory neurons, and decreased NaV1.1 function is hypothesized to reduce GABAergic inhibitory neurotransmission within the brain, driving neuronal network hyperexcitability and subsequent pathology. We have developed a human in vitro model of Dravet syndrome using differentiated neurons derived from patient iPSC and enriched for GABA expressing neurons. Neurons were plated on high definition multielectrode arrays (HD-MEAs), permitting recordings from the same cultures over the 7-weeks duration of study at the network, single cell, and subcellular resolution. Using this capability, we characterized the features of axonal morphology and physiology. Neurons developed increased spiking activity and synchronous network bursting. Recordings were processed through a spike sorting pipeline for curation of single unit activity and to assess the effects of pharmacological treatments. At 7-weeks, the application of the GABAAR receptor agonist muscimol eliminated network bursting, indicating the presence of GABAergic neurotransmission. To identify the role of NaV1.1 on neuronal and network activity, cultures were treated with a dose-response of the NaV1.1 potentiator δ-theraphotoxin-Hm1a. This resulted in a strong increase in firing rates of putative GABAergic neurons, an increase in the intraburst firing rate, and eliminated network bursting. These results validate that potentiation of NaV1.1 in Dravet patient iPSC-derived neurons results in decreased firing synchrony in neuronal networks through increased GABAergic neuron activity and support the use of human neurons and HD-MEAs as viable high-throughput electrophysiological platform to enable therapeutic discovery.

Dataset Information

DeVries2000_PancreaticBetaCells_InsulinSecretion

Publications

Channel sharing in pancreatic beta -cells revisited: enhancement of emergent bursting by noise.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure