Tonic Activation of Presynaptic GABA_B Receptors in the Opener Neuromuscular Junction of Crayfish

Abstract

Release of excitatory transmitter from boutons on crayfish nerve terminals was inhibited by (R,S)-baclofen, an agonist at GABAB receptors. Baclofen had no postsynaptic actions as it reduced quantal content without affecting quantal amplitude. The effect of baclofen increased with concentration producing 18% inhibition at 10 microM; EC50, 50% inhibition at 30 microM; maximal inhibition, 85% at 100 microM and higher. There was no desensitization, even with 200 or 320 microM baclofen. Phaclofen, an antagonist at GABAB receptors, competitively antagonized the inhibitory action of baclofen (KD = 50 microM, equivalent to a pA2 = 4.3 +/- 0.1). Phaclofen on its own at concentrations below 200 microM had no effect on release, whereas at 200 microM phaclofen itself increased the control level of release by 60%, as did 2-hydroxy-saclofen (200 microM), another antagonist at GABAB receptors. This increase was evidently due to antagonism of a persistent level of GABA in the synaptic cleft, since the effect was abolished by destruction of the presynaptic inhibitory fiber, using intra-axonal pronase. We conclude that presynaptic GABAB receptors, with a pharmacological profile similar to that of mammalian GABAB receptors, are involved in the control of transmitter release at the crayfish neuromuscular junction.

Interaction between facilitation and presynaptic inhibition at the crayfish neuromuscular junction

“…Another explanation could be activation of a GABA B receptor. GABA B receptors have been indicated to inhibit transmitter release from crayfish excitor motor terminals (Fischer and Parnas, 1996a,b;Parnas et al, 1999). The apparent persistence of inhibition for a few hundred milliseconds after the offset of inhibitor axon firing (Fig.·2D) would be consistent with the decay of a GABA B -mediated contribution to inhibition.…”

“…Inhibition mediated by GABA B receptors has been reported (Parnas et al, 1999) but we could find no inhibitory effect of baclofen (30-180·µmol·l -1 ; N=4) on excitatory transmission, and baclofen did not occlude inhibition of the EJP by the inhibitor axon nor remove the reduced build-up of facilitation during short trains. Therefore, our data suggest that GABA A -mediated presynaptic inhibition With the inhibitor stimulated in the standard manner (left-hand traces; eight inhibitor stimuli at 100·Hz), inhibition was 13±2% (mean ± S.E.M.…”

Ambient GABA Constrains the Strength of GABAergic Synapses at Cajal-Retzius Cells in the Developing Visual Cortex

“…presynaptic GABA B R-mediated inhibition has also been reported in some other preparations (Le Feuvre et al, 1997;Parnas et al, 1999), suggesting that ambient GABA can suppress synaptic GABA release. In the present study, we have shown that GABA B R activation/block only alters GABA release probability without affecting the RRP or mIPSC amplitudes.…”

Molecular Structure and Physiological Functions of GABABReceptors

“…Although the evidence is still sketchy, it currently appears that most mammalian neurotransmitter receptors have counterparts in invertebrates (337). Invertebrate GABA B receptors were described in echinoderms (90,91), mollusks (11,287), and arthropods (101,226,254,276,335). Invertebrate GABA B functions were mostly studied at the neuromuscular junction of echinoderms, where GABA elicits inhibitory and excitatory responses (90).…”