Energy Metabolism and the Transition Between Epileptiform Activities and Spreading Depression

When nonsynaptic epileptiform activity (NSEA) induced in the dentate gyrus of hippocampus slices (HS) are recorded, the transition to spreading depression (SD) can be seen. During this transition, the interplay of the different ionic species involved and the dynamic mechanisms of action responsible for the ionic homeostasis are too complex to be only experimentally accessed. Thus, we investigated the mechanisms responsible for this transition through the correlation between experimental findings and computational simulations. NSEA were experimentally induced in rat HS in interface chamber. When the slices were perfused with high-potassium (10 mM) and zero-added calcium, the NSEA appeared spontaneously after 1 h. The extracellular potential was recorded in the granule layer. The model describes the electrodiffusion processes of the ionic current through the neuronal and glial membranes and along the extracellular space. Results suggested that the interplay between the influx of Na⁺ through the channels and the Na⁺/K⁺ pump electrogenic currents sustains the NSEA and the transition to SD as well. According to the simulations, the transition from NSEA to SD in particular should occur when there is a failure of the energy metabolism, making the production of ATP insufficient for the maintenance of the Na/K pump activity.