Monoquantal excitatory postsynaptic currents were recorded by means of a perfused macropatch electrode from 9 to 15 micro m stretches of crayfish neuromuscular junctions. The excitatory transmitter l-glutamate superfused to a terminal inhibits quantal release by activating autoreceptors [Parnas et al. (1996) Eur. J. Neurosci., 8, 116-126]. Substances related to glutamate that do not activate glutamatergic postsynaptic channels, but are substrates of glutamate transporters, elicited analogous inhibitions, e.g. l- and d-aspartate and some other glutamate transport blockers. As expected, all transport blockers prolonged synaptic currents. Blockers that bind to the transporter receptors but are not transported did not inhibit release, but prevented inhibition by the transport substrates. It appears that autoinhibition is elicited by transport of glutamate or its analogues. Transport into cells is powered by symport of three Na+. To block the transport step electrochemically, extracellular Na+ concentration was lowered to one-quarter, but this surprisingly left the inhibition of release by glutamate unaffected, showing inhibition to be associated to a step between binding and transport. After binding a substrate, glutamate transporters open a parallel Cl- channel. Replacement of extracellular Cl- prevented Cl- current, and release inhibition by glutamate or aspartate was blocked. It is suggested that the flow of Cl- across the cell membrane, after binding a transport substrate, mediates autoinhibition. We measured a related reduction of presynaptic action potentials.     «

Monoquantal excitatory postsynaptic currents were recorded by means of a perfused macropatch electrode from 9 to 15 micro m stretches of crayfish neuromuscular junctions. The excitatory transmitter l-glutamate superfused to a terminal inhibits quantal release by activating autoreceptors [Parnas et al. (1996) Eur. J. Neurosci., 8, 116-126]. Substances related to glutamate that do not activate glutamatergic postsynaptic channels, but are substrates of glutamate transporters, elicited analogous inh...     »