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

1. Field potential recordings and measurements of the extracellular co ncentration of free K+ ([K+](o)) and Ca2+ ([Ca2+](o)) were made during application of 4-aminopyridine (4-AP, 50 mu M) in hippocampal slices that were obtained from 11- to 32-day-old rats. 2. Spontaneous field p otentials recorded under this experimental condition in the CA3 stratu m radiatum of slices from rats < 23 days old consisted of interictal ( duration, 0.2-1.4 s; intervals of occurrence, 0.9-3.4 s) and ictal epi leptiform discharges (duration, 5-46 s; intervals of occurrence, 22-25 9 s) and negative-going potentials that often preceded the onset of ic tal discharge. Ictal activity became rare in slices: from rats > 25 da ys old. 3. The negative-going potential (which also corresponded to th e ictal discharge onset) was associated with [K+](o) increases to 9.4 +/- 3.6 mM (mean +/- S.D.) from 3.25 mM baseline (n = 11 slices). [K+] (o) remained elevated at 5-6 mM throughout the ictal event. Decreases in [Ca2+](o) (from 1.8 mM baseline to 1.3 +/- 0.1 mM, n = 7) were obse rved during the ictal discharge. 4. Interictal and ictal discharges we re abolished by the non-N-methyl-D-aspartate (NMDA) receptor antagonis t 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 mu M). CNQX and the N MDA receptor antagonist (+/-)-2-carboxypiperazine-4-yl)propyl-1-phosph onic acid (CPP) did not influence negative-going potentials or the ass ociated [K+](o) increases (peak values were 8.7 +/- 3.2 mM, n = 8), th at were blocked, however, by bicuculline methiodide (BMI, 10 mu M). 5. The mu-opioid receptor agonist (D-Ala(2),N-Me-Phe(4),Gly(5)-ol)-enkep halin (DAGO, 10 mu M) which inhibits GABA release from interneurons, p revented the occurrence of both GABA-mediated synchronous potentials a nd subsequent ictal discharges (n = 6) as well as the [K+](o) elevatio ns. DAGO effects were antagonized by naloxone (10 mu M; n = 4). 6. The GABA-mediated [K+](o) elevations changed as a function of age. In hip pocampal slices obtained from 11- to 17-day-old rats, peak values of 1 0.6 +/- 2.0 mM (n = 10) and half-width durations of 8.7 +/- 1.3 s (n = 7) were observed. In slices obtained from 25- to 32-day-old animals t hese parameters were 5.2 +/- 0.5 mM (n = 13) and 4.6 +/- 1.1 s (n = 4) , respectively. 7. This study shows that, in the juvenile rat hippocam pus, 4-AP induces a glutamatergic independent synchronous potential tl :at is due to GABA released from inhibitory terminals and is associate d with an increase in [K+](o). This [K+](o) elevation undergoes age-de pendent changes, and is instrumental in synchronizing neurons thus ini tiating prolonged epileptiform discharges.