4-Aminopyridine-induced synaptic GABAB 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 mumol l-1) in granule cells of guinea-pig hippocampal slices. The responses were recorded in the presence of blockers for glutamatergic and GABAA-receptor-mediated synaptic transmission, 6-cyano-7-nitroquinoxaline-2,3-dione, picrotoxin and bicuculline. The input resistance was much larger (approximately 300 M omega) in tight-seal recording than in sharp-electrode recording (approximately 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.
Jarolimek
W
W
I. Physiologisches Institut, Universität Heidelberg, Germany.
Misgeld
U
U
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004553:Electric Conductivity; D006098:Granulocytes / Q000502:physiology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition; D011188:Potassium / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D011188:Potassium