GABA(B) 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 hi ppocampus were performed to study GABA(B) receptor-mediated inhibition of tetrodotoxin (TTX)-resistant IPSCs. IPSCs were recorded in the pre sence of mt and glutamate receptor antagonists. (R)-(-)-baclofen reduc ed the frequency of TTX-resistant IPSCs by a presynaptic action. The i nhibition by (R)-(-)-baclofen was concentration-dependent, was not mim icked by the less effective enantiomer (S)-(+)-baclofen, and was block ed by the GABA(B) receptor antagonist CGP 55845A, suggesting a specifi c effect on GABA(B) receptors. The inhibition persisted in the presenc e of the Ca2+ channel blocker Cd2+. There was no requirement for an ac tivation of K+ conductances by (R)-(-)-baclofen, because the inhibitio n of TTX-resistant IPSCs persisted in Ba2+ and Cd2+. Because the lime courses of mt-resistant IPSCs were not changed by (R)-(-)-baclofen, th ere was no evidence for a selective inhibition of quantal release from a subgroup of GABAergic terminals. (R)-(-)-baclofen reduced the frequ ency of TTX-resistant IPSCs in guinea pigs and Wistar rats, whereas th e 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 i nhibition by (R)-(-)-baclofen. We conclude that GABA(B) receptors inhi bit TTX-resistant GABA release through a mechanism independent from th e well known effects on Ca2+ or K+ channels. The inhibition of quantal GABA release can be reduced by an activator of protein kinase C.