Changes of Ionic Concentrations During Seizure Transitions - A Modeling Study.
Traditionally, it is considered that neuronal synchronization in epilepsy is caused by a chain reaction of synaptic excitation. However, it has been shown that synchronous epileptiform activity may also arise without synaptic transmission. In order to investigate the respective roles of synaptic interactions and nonsynaptic mechanisms in seizure transitions, we developed a computational model of hippocampal cells, involving the extracellular space, realistic dynamics of [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] ions, glial uptake and extracellular diffusion mechanisms. We show that the network behavior with fixed ionic concentrations may be quite different from the neurons' behavior when more detailed modeling of ionic dynamics is included. In particular, we show that in the extended model strong discharge of inhibitory interneurons may result in long lasting accumulation of extracellular [Formula: see text], which sustains the depolarization of the principal cells and causes their pathological discharges. This effect is not present in a reduced, purely synaptic network. These results point to the importance of nonsynaptic mechanisms in the transition to seizure.
1 Department of Biomedical Physics, Faculty of Physics, University of Warsaw, ul. Pasteura 5, Warsaw, Poland.
Damiano
D
Gentiletti
1 Department of Biomedical Physics, Faculty of Physics, University of Warsaw, ul. Pasteura 5, Warsaw, Poland.
Piotr
P
Suffczynski
2 Unit of Epileptology and Experimental Neurophysiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Giovanni Celoria 11, Milan, Italy.
Vadym
V
Gnatkovsky
2 Unit of Epileptology and Experimental Neurophysiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Giovanni Celoria 11, Milan, Italy.
Marco
M
de Curtis
D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism; D007477:Ions / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D012640:Seizures / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D046509:Tissue Culture Techniques; D000096922:K Cl- Cotransporters
D007477:Ions; D000254:Sodium-Potassium-Exchanging ATPase; D027981:Symporters; D000096922:K Cl- Cotransporters
Potassium; ionic dynamics; modeling; seizures