Presynaptic actions of GABA and baclofen in CA1 region of the guinea-pig hippocampus in vitro.
The presynaptic actions of GABA and (+/-) baclofen on the stratum radiatum in the CA1 region of guinea-pig hippocampal slices were investigated using a modified grease-gap recording technique. D.c. potential shifts were recorded in response to varying concentrations of GABA and (+/-) baclofen. In Ca(2+)-free media containing tetrodotoxin, bath applications of GABA (2.5 microM to 20 mM) produced depolarizations which were concentration-dependent. Maximum depolarization was attained with 10 mM GABA. Superfusion of (+/-) baclofen (0.125-500 microM) produced a concentration-dependent hyperpolarization which peaked at a concentration of 250 microM. The GABA-induced depolarization but not the (+/-) baclofen-induced hyperpolarization was depressed by the GABAA antagonists bicuculline and picrotoxinin. The (+/-) baclofen-induced hyperpolarization but not the GABA-induced depolarization was suppressed by CGP 35,348, a GABAB antagonist. In the presence of bicuculline, GABA (0.5-5.0 mM) occasionally caused a hyperpolarization which could be blocked by CGP 35,348. These results indicate that the primary presynaptic action of GABA on the d.c. potential in the CA1 region of the hippocampus is to produce a GABAA receptor-mediated depolarization, while (+/-) baclofen induces a GABAB receptor-mediated hyperpolarization. The grease-gap d.c. potential recording technique, described in this paper, is expected to be useful in examining changes in the membrane potentials of presynaptic terminals.
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
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Morishita
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Sastry
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D017661:Receptors, Presynaptic / Q000187:drug effects*; D054830:Sesterterpenes; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001418:Baclofen; D001640:Bicuculline; D002118:Calcium; D018756:GABA Antagonists; D009467:Neuromuscular Depolarizing Agents; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D017661:Receptors, Presynaptic; D054830:Sesterterpenes; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; C022961:picrotoxinin