Block of GABA-transaminase modifies GABAergic transmission at the crayfish synapses.

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of ethanolamine-O-sulfate (EOS), a gamma-aminobutyric acid (GABA)-transaminase blocker, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish opener neuromuscular synapses. 2. Intracellular recordings of evoked excitatory (EPSPs) and inhibitory postsynaptic potentials (IPSPs) as well as loose macropatch clamp measurements of excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs) were used to evaluate the effects of the drug, which was applied exclusively to the nerve bundle. 3. Under normal conditions, a stimulus train to the inhibitor before the excitor stimulation elicited two phases of inhibition: 1) a large reduction in EPSP amplitude associated with a decrease in its time constant of decay (tau D) at time intervals of 0-15 ms and 2) a moderate decrease in EPSP amplitude with a small change in EPSP tau D at intervals of 15-90 ms. EOS treatment selectively increased the inhibition of phase 2. 4. The muscle membrane electrical parameters and the existing postsynaptic tonic release of GABA were not affected by the drug. 5. EOS did not alter the IPSP's parameters such as amplitude, reversal potential, and conductance. 6. Quantal analysis of single IPSCs revealed no significant changes in the statistical parameters such as quantum size (q), quantal content (m), number of active zones (n), or probability of release (p). 7. Quantal analysis of EPSCs, released after interaction with the inhibitor, did exhibit a large reduction in m without any effect on q. 8. These results demonstrate that EOS has a specific and differential effect on neural transmission in two synapses of the same axon: it increases presynaptic inhibition without significant effect on the postsynaptic inhibitory mechanism.