GABAB receptor-mediated inhibition of spontaneous inhibitory synaptic currents in rat midbrain culture.
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.
Rohrbacher
J
J
I. Institute of Physiology, University of Heidelberg, Germany.
Jarolimek
W
W
Lewen
A
A
Misgeld
U
U
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002121:Calcium Channel Blockers; D018755:GABA Agonists; D007473:Ion Channels; D015221:Potassium Channels; D018080:Receptors, GABA-B; D015222:Sodium Channels; D010566:Virulence Factors, Bordetella; D002104:Cadmium; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D037342:Pertussis Toxin; D001418:Baclofen