4-AMINOPYRIDINE-INDUCED SYNAPTIC GABA(B) CURRENTS IN GRANULE CELLS OF THE GUINEA-PIG HIPPOCAMPUS

Sharp-electrode and tight-seal perforated-patch and whole-cell recording techniques were used to evaluate K+-dependent inhibitory postsynaptic potentials (K-IPSPs) and currents (K-IPSCs) induced by the convulsant 4-aminopyridine (50 mu mol 1(-1)) in granule cells of guinea-pig hippocampal dices. The responses were recorded in the presence of blockers for glutamatergic and GABA(A)-receptor-mediated synaptic transmission, 6-cyano-7-nitroquinoxaline-2,3-dione, picrotoxin and bicuculline. The input resistance was much larger (approximate to 300 M Omega) in tight-seal recording than in sharp-electrode recording (approximate to 100 M Omega), but the amplitudes of K-IPSPs recorded at -65 mV holding potential were similar in all three recording configurations. The 4-aminopyridine-induced currents reversed near the K+ equilibrium potential, and the reversal potentials shifted with changes in [K+](out) or [K+](in) as expected for a K+ current. Slope conductance measurements indicated a conductance increase during the peak of the K-IPSP up to 5 nS (mean 2.4 nS). The peak conductance was underestimated in whole-cell recordings unless the pipette contained Cs'. Considering the high membrane resistance of granule cells, K-IPSCs induced by 4-aminopyridine hyperpolarize the cells considerably and thereby are likely to contribute to the failure of 4-aminopyridine to induce burst discharges in granule cells.