Extracellular free potassium during synchronous activity induced by 4-aminopyridine in the juvenile rat hippocampus

Abstract

Field potential recordings and measurements of the extracellular concentration of free K + ([K + 0]) were made in the stratum radiatum of the CA3 subfield of hippocampal slices that were obtained from 12- to 17-day-old rats. Spontaneous, synchronous field potentials were recorded in the presence of the convulsant drug 4-aminopyridine (4AP, 50 μM). They consisted of interictal- (duration = 0.2−1.2 s; rate of occurrence = 0.3−1.3 Hz) and ictal-like epileptiform discharges (8–40 s; 4−38·10 −3 Hz), as well as large amplitude, negative-going potentials that preceded the onset of the ictal-like event. Such a temporal correlation suggested that the negative-going potential might facilitate the onset of ictal-like activity. Interictal- and ictal-like discharges were abolished by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM), while the negative-going potential was selectively blocked by bicuculline methiodide (BMI, 10 μM). Hence it was presumably due to the activation of GABA A receptors. [K +] 0 increased up to 12.5 mM (7.9 ± 2.7 mM, mean ± S.D.) from a resting value of 3.25 mM during the BMI-sensitive potentials (which also corresponded to the onset of ictal-like events), and after a decline to approximately 5 mM it remained elevated throughout the ictal event. Small, transient increases in [K +] 0 (up to 3.7 mM) could be seen during each interictal-like event. Following blockade of interictal- and ictal-like discharges by CNQX increases in [K +] 0 (up to 11 mM; 7.3 ± 2.1; half-width = 7.2 ± 2.3 s) still accompanied the BMI-sensitive negative-going potentials. Our findings indicate that the negative-going synchronous potential induced by 4AP is associated with an increase in [K +] 0 that is presumably due to the activation of GABA A receptors. Such a mechanism might be instrumental in synchronizing neurons and thus facilitate the onset of prolonged epileptiform discharges.