CGP 55845A blocks baclofen, gamma-aminobutyric acid and inhibitory postsynaptic potassium currents in guinea pig CA3 neurons.
Single electrode voltage-clamp recording from CA3 neurons in guinea pig hippocampal slices was applied to study effects of a new GABAB antagonist, CGP 55845A, on (-)baclofen (IBac)- or gamma-aminobutyric acid (IGABA)-induced potassium (K)-currents and on inhibitory postsynaptic K-currents (K-IPSCs) recorded in the presence of blockers for fast synaptic transmission. K-IPSCs were induced by bath application of 4-amino-pyridine (4-AP). CGP 55845A, in 10(-8) to 10(-7) M concentrations, blocked all these K-currents and was more potent than all GABAB antagonists known to date. However, onset of the CGP 55845A effect and recovery were slow. We conclude that a potent and selective GABAB antagonist is now available to study the physiological role of GABAB receptors in the mammalian brain.
Jarolimek
W
W
I. Physiologisches Institut, Universität Heidelberg, FRG.
Demmelhuber
J
J
Bijak
M
M
Misgeld
U
U
D015761:4-Aminopyridine / Q000378:metabolism; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004594:Electrophysiology; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D015761:4-Aminopyridine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001418:Baclofen; D001640:Bicuculline; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D015221:Potassium Channels; D011810:Quinoxalines; D005680:gamma-Aminobutyric Acid