EXTRACELLULAR FREE POTASSIUM DURING SYNCHRONOUS ACTIVITY-INDUCED BY 4-AMINOPYRIDINE IN THE JUVENILE RAT HIPPOCAMPUS

Field potential recordings and measurements of the extracellular conce ntration 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-d ay-old rats. Spontaneous, synchronous field potentials were recorded i n the presence of the convulsant drug 4-aminopyridine (4AP, 50 mu M). They consisted of interictal- (duration = 0.2-1.2 s; rate of occurrenc e = 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 tha t preceded the onset of the ictal-like event. Such a temporal correlat ion suggested that the negative-going potential might facilitate the o nset of ictal-like activity. Interictal- and ictal-like discharges wer e abolished by the AMPA/kainate receptor antagonist 6-cyano-7-nitroqui noxaIine-2,3-dione (CNQX, 10 pM), while the negative-going potential w as selectively blocked by bicuculline methiodide (BMI, 10 mu M). 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 restin g value of 3.25 mM during the BMI-sensitive potentials (which also cor responded to the onset of ictal-like events), and after a decline to a pproximately 5 mM it remained elevated throughout the ictal event. Sma ll, transient increases in [K+](0) (up to 3.7 mM) could be seen during each interictal-like event. Following blockade of interictal- and ict al-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 n egative-going potentials. Our findings indicate that the negative-goin g synchronous potential induced by 4AP is associated with an increase in [K+](0) that is presumably due to the activation of GABA(A) recepto rs. Such a mechanism might be instrumental in synchronizing neurons an d thus facilitate the onset of prolonged epileptiform discharges.