GABAB receptor-mediated inhibition of spontaneous inhibitory synaptic currents in rat midbrain culture

• Published in: The Journal of physiology Vol. 500; no. Pt 3; pp. 739 - 749
• Main Authors: Rohrbacher, J, Jarolimek, W, Lewen, A, Misgeld, U
• Format: Journal Article
• Language: English
• Published: England The Physiological Society 01.05.1997
• Subjects: Animals; Baclofen - pharmacology; Cadmium - pharmacology; Calcium Channel Blockers - pharmacology; Cells, Cultured; Electrophysiology; GABA Agonists - pharmacology; gamma-Aminobutyric Acid - metabolism; Ion Channels - drug effects; Ion Channels - physiology; Membrane Potentials - physiology; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - physiology; Patch-Clamp Techniques; Pertussis Toxin; Potassium Channels - drug effects; Potassium Channels - metabolism; Rats; Rats, Wistar; Receptors, GABA-B - drug effects; Receptors, GABA-B - physiology; Sodium Channels - drug effects; Sodium Channels - metabolism; Synapses - drug effects; Synapses - physiology; Tetrodotoxin - pharmacology; Virulence Factors, Bordetella - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1997.sp022055

1. Tight-seal, whole-cell recording was used to study GABAB receptor-mediated inhibition of spontaneous inhibitory synaptic currents in cultured rat midbrain neurones. 2. Spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were recorded in tetrodotoxin (TTX), Cd2+ and Ba2+. (R)-(-)-baclofen reduced the frequency of mIPSCs through a presynaptic mechanism. The EC50 for this effect was 7 microM. It was antagonized by the GABAB receptor antagonist CGP55845A (0.5 microM). 3. In pertussis toxin (PTX)-treated cultures, some GABAB receptor-mediated reduction of the frequency of mIPSCs persisted. In contrast, PTX treatment totally abolished inhibition of miniature excitatory postsynaptic currents (mEPSCs). 4. In PTX-treated cultures, a saturating concentration of (R)-(-)-baclofen inhibited action potential-generated IPSCs but no EPSCs. 5. PTX treatment abolished the (R)-(-)-baclofen-mediated inhibition of high voltage-activated somatic Ca2+ currents and of spontaneous IPSCs depending on presynaptic Ca2+ entry. 6. We conclude that cellular mechanisms underlying GABAB receptor-mediated inhibition of mIPSCs contribute to auto-inhibition of GABA release.