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.

journal_name

Phys Biol

journal_title

Physical biology

authors

Lopes MR,Santos LE,Rodrigues AM,Duarte MA,Infantosi AF,Scorza FA,Arida RM,Madureira AP,da Silveira GA,dos Santos IC,Cavalheiro EA,de Almeida AC

doi

10.1088/1478-3975/10/5/056008

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

056008

issue

5

eissn

1478-3967

issn

1478-3975

journal_volume

10

pub_type

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