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Effect of co-transporter blockers on non-synaptic epileptiform activity-computational simulation.

Abstract
The important role of cation-chloride co-transporters in epilepsy is being supported by an increasing number of investigations. However, enormous complexity is involved since the action of these co-transporters has effects on the ionic homeostasis influencing directly the neuronal excitability and the tissue propensity to sustain seizure. To unravel the complex mechanisms involving the co-transporters action during seizure, this paper shows simulations of non-synaptic epileptiform activity and the effect of the blockage of the two different types of cation-chloride co-transporters present in the brain: Na, K and 2Cl co-transporter (NKCC) and K and Cl co-transporter (KCC). The simulations were performed with an electrochemical model representing the non-synaptic structure of the granule cell layer of the dentate gyrus (DG) of the rat hippocampus. The simulations suggest: (i) the potassium clearance is based on the systemic interplay between the Na/K pump and the NKCC co-transporters; (ii) the simultaneous blockage of the NKCC of the neurons and KCC of glial cells acts efficiently suppressing the epileptiform activities; and (iii) the simulations show that depending on the combined blockage of the co-transporters, the epileptiform activities may be suppressed or enhanced.
AuthorsMariana Rodrigues Lopes, Luiz Eduardo Canton Santos, Antônio Márcio Rodrigues, Mario Antônio Duarte, Antonio Fernando Catelli Infantosi, Fulvio Alexandre Scorza, Ricardo Mario Arida, Ana Paula Madureira, Gilcélio Amaral da Silveira, Ivans Carlos dos Santos, Esper Abrão Cavalheiro, Antônio-Carlos Guimarães de Almeida
JournalPhysical biology (Phys Biol) Vol. 10 Issue 5 Pg. 056008 (Oct 2013) ISSN: 1478-3975 [Electronic] England
PMID24092000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Sodium-Potassium-Chloride Symporters
  • Symporters
  • potassium-chloride symporters
Topics
  • Animals
  • Computer Simulation
  • Electroencephalography
  • Epilepsy (drug therapy, physiopathology)
  • Hippocampus (drug effects, physiopathology)
  • Neurons (drug effects, physiology)
  • Rats
  • Sodium-Potassium-Chloride Symporters (drug effects)
  • Symporters (antagonists & inhibitors)

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