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

Abstract

Tonic activation of presynaptic GABAB receptors in the opener neuromuscular junction of crayfish. 1184–1191 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 μM; EC50, 50% inhibition at 30 μM; maximal inhibition, 85% at 100 μM and higher. There was no desensitization, even with 200 or 320 μM baclofen. Phaclofen, an antagonist at GABABreceptors, competitively antagonized the inhibitory action of baclofen ( K D = 50 μM, equivalent to a pA2 = 4.3 ± 0.1). Phaclofen on its own at concentrations below 200 μM had no effect on release, whereas at 200 μM phaclofen itself increased the control level of release by 60%, as did 2-hydroxy-saclofen (200 μM), 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.