Differential activation of two distinct mechanisms for presynaptic inhibition by a single inhibitory axon.

1. Presynaptic inhibition of excitatory transmitter release evoked by inhibitory axon stimulation was studied at individual release boutons of the crayfish opener neuromuscular junction. 2. Presynaptic inhibition was maximal (approximately 30%) when a single inhibitory action potential preceded the excitatory test action potential by 1-2 ms. This inhibition lasted at most 5 ms. It was blocked by 50 microM picrotoxin, and is probably mediated mainly by gamma-aminobutyric acid-A (GABAA) receptors. 3. Presynaptic inhibition produced by a brief train of inhibitory action potentials (5 pulses at 100 Hz) was maximal (approximately 60%) when the last inhibitory action potential (of the train) preceded the excitatory test action potential by 10 ms. This inhibition lasted up to 50 ms. It seems that in this case GABAB receptors were activated as well, because the combined action of picrotoxin (50 microM) and 20H-Saclofen (100 microM) was required to block the inhibition. 4. We thus show that one and the same inhibitory release bouton can differentially activate two distinct mechanisms for presynaptic inhibition by activating GABAA and GABAB receptors.