Extracellular potassium elevations in the hippocampus of rats with long-term pilocarpine seizures

Abstract

Pilocarpine injection into rodents leads to the development of chronic limbic seizures that follow an initial status epilepticus and a seizure-free interval. It has been proposed that a decreased efficacy of the mechanisms that buffer the extracellular concentration of K + ([K +] o) leads to an increase in seizure susceptibility. Therefore, we analyzed the changes in [K +] o associated with the synchronous activity induced by 4-aminopyridine (4AP) in hippocampal slices obtained from control and pilocarpine-treated rats. At all recording sites (i.e. stratum radiatum of the CA1 and CA3 subfields, and hilus of the dentate gyrus), the amplitude of GABA-mediated synchronous field potentials induced by 4AP, as well as the associated [K +] o increases, were significantly reduced in slices obtained from the pilocarpine-treated rats. In the control group, the field-potential amplitudes reached 1 mV (i.e. 1.7 ± 0.3 mV in CA1, 0.93 ± 0.2 mV in CA3, and 1.03 ± 0.12 mV in the hilus; mean ± SEM), while the accompanying rises in [K +] o exceeded 4 mM (i.e. 4.17 ± 0.15 mM in CA1, 4.04 ± 0.12 mM in CA3, 4.04 ± 0.11 mM in the hilus) from a baseline of 3.25 mM. The corresponding values in slices from the pilocarpine-treated group were rarely greater than 0.4 mV (i.e. 0.3 ± 0.09 mV in CA1, 0.27 ± 0.03 mV in CA3 and 0.38 ± 0.06 mV in the hilus), and larger than 3.6 mM (i.e. 3.63 ± 0.04 mM in CA1, 3.64 ± 0.03 mM in CA3 and 3.60 ± 0.04 mM in the hilus) from a similar baseline value. With pilocarpine, the rate of occurrence of the GABA-mediated potential significantly decreased from 0.035 to 0.016 s −1. Since the rises in [K +] o decreased rather than increased and their overall duration was unchanged (possibly reflecting cell loss), we conclude that a modification of [K +] o buffering capacity is unlikely to account for the appearance of in vivo seizures in the pilocarpine model of epilepsy.