Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state-Computational simulation

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Almeida, Antonio-Carlos G. de
Rodrigues, Antonio M.
Scorza, Fulvio A. [UNIFESP]
Cavalheiro, Esper Abrão [UNIFESP]
Teixeira, Hewerson Z.
Duarte, Mario A.
Silveira, Gilcelio A.
Arruda, Emerson Z.
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The aim of this work is to study, by means of computational simulations, the induction and sustaining of nonsynaptic epileptiform activity.The computational model consists of a network of cellular bodies of neurons and glial cells connected to a three-dimensional (3D) network of juxtaposed extracellular compartments. the extracellular electrodiffusion calculation was used to simulate the extracellular potential. Each cellular body was represented in terms of the transmembrane ionic transports (Na(+)/K(+) pumps, ionic channels, and cotransport mechanisms), the intercellular electrodiffusion through gap-junctions, and the neuronal interaction by electric field and the variation of cellular volume.The computational model allows simulating the nonsynaptic epileptiform activity and the extracellular potential captured the main feature of the experimental measurements. the simulations of the concomitant ionic fluxes and concentrations can be used to propose the basic mechanisms involved in the induction and sustaining of the activities.The simulations suggest: the bursting induction is mediated by the Cl(-) Nernst potential overcoming the transmembrane potential in response to the extracellular [K(+)] increase. the burst onset is characterized by a critical point defined by the instant when the Na(+) influx through its permeable ionic channels overcomes the Na(+)/K(+) pump electrogenic current. the burst finalization is defined by another critical point, when the electrogenic current of the Na(+)/K(+) pump overcomes its influx through the channels.
Epilepsia. Malden: Wiley-Blackwell, v. 49, n. 11, p. 1908-1924, 2008.