GABAB receptor-mediated inhibition of tetrodotoxin-resistant GABA release in rodent hippocampal CA1 pyramidal cells.
Tight-seal whole-cell recordings from CA1 pyramidal cells of rodent hippocampus were performed to study GABAB receptor-mediated inhibition of tetrodotoxin (TTX)-resistant IP-SCs. IPSCs were recorded in the presence of TTX and glutamate receptor antagonists. (R)-(-)-baclofen reduced the frequency of TTX-resistant IPSCs by a presynaptic action. The inhibition by (R)-(-)-baclofen was concentration-dependent, was not mimicked by the less effective enantiomer (S)-(+)-baclofen, and was blocked by the GABAB receptor antagonist CGP 55845A, suggesting a specific effect on GABAB receptors. The inhibition persisted in the presence of the Ca2+ channel blocker Cd2+. There was no requirement for an activation of K+ conductances by (R)-(-)-baclofen, because the inhibition of TTX-resistant IPSCs persisted in Ba2+ and Cd2+. Because the time courses of TTX-resistant IPSCs were not changed by (R)-(-)-baclofen, there was no evidence for a selective inhibition of quantal release from a subgroup of GABAergic terminals. (R)-(-)-baclofen reduced the frequency of TTX-resistant IPSCs in guinea pigs and Wistar rats, whereas the inhibition was much smaller in Sprague Dawley rats. In Cd2+ and Ba2+, beta-phorbol-12,13-dibutyrate and forskolin enhanced the frequency of TTX-resistant IPSCs. Only beta-phorbol-12, 13-dibutyrate reduced the inhibition by (R)-(-)-baclofen. We conclude that GABAB receptors inhibit TTX-resistant GABA release through a mechanism independent from the well known effects on Ca2+ or K+ channels. The inhibition of quantal GABA release can be reduced by an activator of protein kinase C.
Jarolimek
W
W
Institute of Physiology, University of Heidelberg, Germany.
Misgeld
U
U
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004351:Drug Resistance; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D011188:Potassium / Q000502:physiology; D011493:Protein Kinase C; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism*
D018755:GABA Agonists; D018080:Receptors, GABA-B; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011493:Protein Kinase C; D001418:Baclofen; D011188:Potassium; D002118:Calcium