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 to study responses elicited by (-)baclofen or gamma-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 microM), bicuculline (50 microM), and picrotoxin (50 microM). (-)Baclofen (0.5 microM) 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 induced K-IPSPs or IPSCs) reversed in sign near the K-equilibrium potential (EK). The GABAB receptor antagonists, OH-saclofen (500 microM) and CGP 35348 (100 microM), reduced (-)baclofen responses, and 4-AP induced K-IPSPs, suggesting that they were mediated by GABAB receptors. Intracellular tetraethylammonium-, and extracellular barium-ions (1 mM) 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 K-IPSCs were not blocked by intracellular Cs-ions. Extracellular Cs-ions (5 mM) 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 activated by (-)baclofen or the endogenous transmitter GABA.(ABSTRACT TRUNCATED AT 250 WORDS)
I. Physiologisches Institut, Universität Heidelberg, Germany.
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Jarolimek
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M
Bijak
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U
Misgeld
D015761:4-Aminopyridine / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*
D000631:Aminopyridines; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D015221:Potassium Channels; D018080:Receptors, GABA-B; C066430:CGP 35348; D015761:4-Aminopyridine; D001418:Baclofen; C080629:saclofen