• GABAB receptor antagonists;
  • K-channel blockers;
  • Hippocampal slice;
  • Baclofen;
  • K-IPSP


Single-electrode current- and voltage-clamp techniques were employed to study responses elicited by (−)baclofen or γ-aminobutyric acid (GABA) and 4-aminopyridine (4-AP) induced inhibitory postsynaptic potentials in CA3 pyramidal neurons in guinea pig hippocampal slices. All drugs were applied by the bath to submerged slices in which fast synaptic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (10 μM), bicuculline (50 μM), and picrotoxin (50 μM). (−)Baclofen (0.5 μM) and GABA (1 μM) induced equivalent-sized hyperpolarizations and input resistance decreases. The agonist induced hyperpolarization or current and 4-AP induced hyperpolarizations or currents (4-AP induced K-IPSPs or IPSCs) reversed in sign near the K-equilibrium potential (EK). The GABAB receptor antagonists, OH-saclofen (500 μM) and CGP 35348 (100 μM), reduced (−)baclofen responses, and 4-AP induced K-IPSPs, suggesting that they were mediated by GABAB receptors. Intracellular tetraethylammonium-, and extracellular barium-ions (1 μM) diminished the (−)baclofen induced current and 4-AP induced K-IPSCs. Intracellular Cs-ions blocked the (−)baclofen induced outward current at resting membrane potential but did not grossly affect the inward current recorded at membrane potentials negative to EK. 4-AP induced inwardly or outwardly directed KIPSCs were not blocked by intracellular Cs-ions. Extracellular Cs-ions (5 μM) blocked the (−)baclofen induced inward K-current, but did not block 4-AP induced inwardly directed K-IPSCs. In conclusion, we found differences in the Cs block of K-channels activated by (−)baclofen or the endogenous transmitter GABA. One reason could be that (−)baclofen predominantly activated extra synaptic GABAB receptors provided that extrasynaptic and subsynaptic receptors couple to different potassium channels. © 1994 Wiley-Liss, Inc.