Post-traumatic hyperexcitability is not caused by impaired buffering of extracellular potassium.

Impaired extracellular potassium buffering has been proposed as one of the major mechanisms underlying the increased risk for temporal lobe epilepsy after brain injury (D'Ambrosio et al., 1999). The present study systematically tested this hypothesis by measuring the resting [K+]o and recovery of the stimulation-evoked [K+]o increases in the dentate gyrus after experimental head trauma, using a combination of whole-cell recordings and ion-selective microelectrode recordings in rat hippocampal slices. Despite the presence of hyperexcitability, the resting [K+]o was not increased after injury. The faster rate of increase and larger amplitude of the orthodromically evoked [K+]o elevation after head trauma occurred in association with a greater population spike with shorter response latency. Contrary to the assumption in previous studies that the evoked activity in control and injured neuronal circuits is the same during antidromic activation, stimulation of granule cell axons in glutamate receptor antagonists evoked a greater [K+]o increase and a larger population spike. Although perforant path stimulation resulted in a larger [K+]o elevation after injury, the rate of clearance of the [K+]o transients evoked either by neuronal activity or by external application of potassium was not compromised. The [K+]o increase evoked by activation of the presynaptic afferents in isolation was not increased. In addition, the postsynaptic neuronal depolarization and firing evoked by exogenous potassium application was decreased after trauma. These results show that the regulation of [K+]o is not impaired after injury and indicate that the larger [K+]o increase evoked by neuronal activity is a consequence, rather than the primary mechanism underlying post-traumatic hyperexcitability.