Abstracts

NETWORK MODELS OF SEIZURE DYNAMICS: IMPORTANCE OF CALCIUM CLEARANCE SYSTEMS

Abstract number : IW.13
Submission category : 1. Translational Research
Year : 2008
Submission ID : 8616
Source : www.aesnet.org
Presentation date : 12/5/2008 12:00:00 AM
Published date : Dec 4, 2008, 06:00 AM

Authors :
Pawel Kudela, W. Anderson, Piotr Franaszczuk and G. Bergey

Rationale: The large neuronal depolarizations associated with epileptic events lead to a significant influx of Ca2+ into neurons. Ca2+ ions are involved in the regulation of many intracellular processes and therefore Ca2+ dynamics and clearance mechanisms may have a significant impact on seizure evolution. In this computational study we investigate how periods of long and recurrent neuronal bursting affect seizure dynamics. Methods: Calcium dynamics are simulated in a spherical neuron model incorporating Ca2+ influx, diffusion, buffering, and extrusion. The neuron model is composed of nine concentric shells, a core, an extrusion pump, and includes two buffer systems intended to represent mobile and immobile intrinsic Ca2+ buffers. We use a spatially distributed array of interconnected spherical neurons capable of reproducing recurrent bursting activity and the behaviours consistent with human seizures. Results: Simulated Ca2+ dynamics have two components: a fast component associated with rapid Ca2+ changes following APs and a slow component resulting from Ca2+ redistribution inside neurons. The first is determined by Ca2+ diffusion processes and fast buffering while the latter depends on characteristics of immobile buffers. Repetitive neuronal bursting, representing seizure-like activity in the network, alters the distribution of fast buffers and the concentration of slow buffers in neurons. Once periodic bursting is established in the network, the baseline of the free mobile buffer concentration in neurons decreases over time in a spatially nonuniform manner. This affects the fast buffer gradient concentration, which in turn impacts the Ca2+ diffusion process. The direction of Ca2+ transport inside neurons changes over the time course of the simulated neuronal bursting. The diffusion of Ca2+ ions from the upper into the deeper shells at the beginning is later reversed as Ca-bound fast buffers begin to flow in the opposite direction. The concentration of free slow immobile buffers shows a hyperbolic decrease in time with the fastest rate of decrease in the outermost shell. Typically after 200 seconds the concentration of slow and fast buffers stabilizes at new resting levels. Conclusions: This network model study throws light the on complex Ca2+ dynamics during simulated epileptiform activity. Throughout the duration of the simulation the concentration of fast and slow free buffers show a hyperbolic decreases in time. Inside a neuron, the rate of the buffer concentration decrease is not uniform. The process of Ca2+ buffers redistribution may produce gradients in buffer concentration affecting the direction of Ca2+ diffusion in neurons. The characteristic time of the Ca2+ buffer redistribution process in a neuron after the induction of recurrent bursting in the network is consistent with the duration of seizures in humans. Supported by NIH grand NS51382
Translational Research