DIFFERENCES IN THE CS BLOCK OF BACLOFEN AND 4-AMINOPYRIDINE INDUCED POTASSIUM CURRENTS OF GUINEA-PIG CA3 NEURONS IN-VITRO

Single-electrode current- and voltage-clamp techniques were employed t o study responses elicited by (-)baclofen or gamma-aminobutyric acid ( GABA) and 4-aminopyridine (4-AP) induced inhibitory postsynaptic poten tials in CA3 pyramidal neurons in guinea pig hippocampal slices. All d rugs were applied by the bath to submerged slices in which fast synapt ic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (1 0 mu M), bicuculline (50 mu M), and picrotoxin (50 mu M). (-)Baclofen (0.5 mu M) and GABA (1 mM) induced equivalent-sized hyperpolarizations and input resistance decreases. The agonist induced hyperpolarization or current and 4-AP induced hyperpolarizations or currents (4-AP indu ced K-IPSPs or IPSCs) reversed in sign near the K-equilibrium potentia l (E(K)). The GABA(B) receptor antagonists, OH-saclofen (500 mu M) and CGP 35348 (100 mu M), reduced (-)baclofen responses, and 4-AP induced K-IPSPs, suggesting that they were mediated by GABA(B) receptors. Int racellular tetraethylammonium-, and extracellular barium-ions (1 mM) d iminished the (-)baclofen induced current and 4-AP induced K-IPSCs. In tracellular Cs-ions blocked the(-)baclofen induced outward current at resting membrane potential but did not grossly affect the inward curre nt recorded at membrane potentials negative to E(K). 4-AP induced inwa rdly or outwardly directed K-IPSCs were not blocked by intracellular O s-ions. Extracellular Cs-ions (5 mM) blocked the (-)baclofen induced i nward K-current, but did not block 4-AP induced inwardly directed K-IP SCs. In conclusion, we found differences in the Os block of K-channels activated by (-)baclofen or the endogenous transmitter GABA. One reas on could be that (-)baclofen predominantly activated extrasynaptic GAB A(B) receptors provided that extrasynaptic and subsynaptic receptors c ouple to different potassium channels. (C) 1994 Wiley-Liss, Inc.