GABA enhances transmission at an excitatory glutamatergic synapse.

GABA mediates both presynaptic and postsynaptic inhibition at many synapses. In contrast, we show that GABA enhances transmission at excitatory synapses between the lateral gastric and medial gastric motor neurons and the gastric mill 6a and 9 (gm6a, gm9) muscles and between the lateral pyloric motor neuron and pyloric 1 (p1) muscles in the stomach of the lobster Homarus americanus. Two-electrode current-clamp or voltage-clamp techniques were used to record from muscle fibers. The innervating nerves were stimulated to evoke excitatory junctional potentials (EJPs) or excitatory junctional currents. Bath application of GABA first decreased the amplitude of evoked EJPs in gm6a and gm9 muscles, but not the p1 muscle, by activating a postjunctional conductance increase that was blocked by picrotoxin. After longer GABA applications (5-15 min), the amplitudes of evoked EJPs increased in all three muscles. This increase persisted in the presence of picrotoxin. beta-(Aminomethyl)-4-chlorobenzenepropanoic acid (baclofen) was an effective agonist for the GABA-evoked enhancement but did not increase the postjunctional conductance. Muscimol activated a rapid postsynaptic conductance but did not enhance the amplitude of the nerve-evoked EJPs. GABA had no effect on iontophoretic responses to glutamate and decreased the coefficient of variation of nerve-evoked EJPs. In the presence or absence of tetrodotoxin, GABA increased the frequency but not the amplitude of miniature endplate potentials. These data suggest that GABA acts presynaptically via a GABA(B)-like receptor to increase the release of neurotransmitter.