Role of potassium lateral diffusion in non-synaptic epilepsy: a computational study.
An increase of extracellular potassium ion concentration can result in neuronal hyperexcitability, and thus contribute to non-synaptic epileptiform activity. It has been shown that potassium lateral diffusion alone is sufficient for synchronization in the low-calcium epilepsy in-vitro model. However, it is not yet known whether the lateral diffusion can, by itself, induce seizure activity. We hypothesize that spontaneous sustained neuronal activity can be generated by potassium coupling between neurons. To test this hypothesis, neuronal simulations with 2-cell or 4-cell models were used. Each model neuron was embedded in a bath of K+ and surrounded by interstitial space. Interstitial potassium concentration was regulated by both K+-pump and glial buffer mechanisms. Simulations performed with two coupled neurons with parameter values within physiological range show that, without chemical and electrical synapses, potassium lateral diffusion alone can generate and synchronize zero-Ca2+ non-synaptic epileptiform activity. Simulations performed with a network of four zero-Ca2+ CA1 pyramidal neurons modeled in zero-calcium conditions also show that spontaneous sustained activity can propagate by potassium lateral diffusion alone with a velocity of approximately 0.93 mm/sec. This diffusion model used for the simulations is based on physiological parameters, is robust for various kinetics, and is able to reproduce both the spontaneous triplet bursting of non-synaptic activity and speed of propagation in low-Ca2+ non-synaptic epilepsy experiments. These simulations suggest that potassium lateral diffusion can play an important role in the synchronization and generation on non-synaptic epilepsy.
Park
Eun-Hyoung
EH
Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Room 112 Wickenden Bldg., Cleveland, OH 44106-4912, USA.
Durand
Dominique M
DM
D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D004058:Diffusion; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*
D011188:Potassium; D002118:Calcium