Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the ratsupraoptic nucleus: role of N- and P/Q-type calcium channels

1. We previously reported that oxytocin (OXT), released from the dendrites of magnocellular neurons in the supraoptic nucleus (SON), acts retrogradely on presynaptic terminals to inhibit glutamatergic transmission. Here we te st the hypothesis that oxytocin reduces calcium influx into the presynaptic : terminal. 2. We used nystatin perforated-patch recording in vitro to first identify t he calcium channels involved in glutamatergic transmission in the SON. omeg a -Conotoxin GVIA (omega -CTx) and omega -Agatoxin TK (omega -Aga) both red uced evoked EPSC amplitude, while nicardipine and nickel had no effect. A c ombination of omega -CTx and omega -Aga completely abolished the evoked EPS Cs. 3. This depressant effect was accompanied by an increase in the paired puls e ratio with no change in the kinetics of the evoked EPSCs, AMPA currents o r postsynaptic cell properties. These results suggest that presynaptic N- a nd P/Q-type calcium channels mediate glutamate release in the SON while L-, T- and R-type channels make little or no contribution. 4. Oxytocin-induced reduction of the evoked EPSC was substantially occluded in the presence of omega -CTx but only partially in the presence of omega -Aga. 5. Amastatin, an endopeptidase inhibitor that increases the level of endoge nous OXT, also reduced the evoked EPSC. This amastatin effect was also occl uded by omega -CTx and omega -Aga. 6. Miniature EPSCs, which are independent of extracellular calcium, were un affected by either omega -CTx or by OXT, thus further substantiating an act ion of both compounds on calcium channels. 7. Therefore, dendritically released oxytocin acts mainly via a mechanism i nvolving the N-type channel, and to a lesser extent the P/Q-type channel, t o decrease excitatory transmission.