Effects of steroids on NMDA receptors and excitatory synaptic transmissionin neonatal motoneurons in rat spinal cord slices

The effect of steroids on NMDA receptors and excitatory postsynaptic transm ission was studied in fluorescence-labelled motoneurons in thin spinal cord slices. In outside-out patches, NMDA-induced responses were potentiated by 79% in the presence of 20-oxopregn-5-en-3 beta -yl sulfate (PS), while in the presence of 20-oxo-5 alpha -pregnan-3 alpha -yl sulfate (3 alpha5 alpha S) and 20-oxo-5 beta -pregnan-3 alpha -yl sulfate (3 alpha5 betaS) they wer e diminished by 57% and 66%, respectively. PS and 3 alpha5 betaS had no eff ect on the amplitude of single NMDA receptor channel openings, however, bot h compounds altered relative distribution of the openings to individual con ductance levels. In control cases, the most frequent openings of the NMDA r eceptor channels were at the 70 pS conductance level, while in the presence of PS or 3 alpha5 betaS, the most frequent openings were at the 55 pS cond uctance level. Analysis of the mean current transferred by NMDA receptor ch annel openings at individual conductance levels indicated that in the prese nce of PS, the mean current induced by 55 pS conductance openings was signi ficantly increased. In the presence of 3 alpha5 betaS, the mean currents in duced by 55 pS and 70 pS conductance openings were significantly decreased. The amplitude of NMDA receptor-mediated EPSCs was potentiated by 54% in th e presence of PS and the deactivation kinetics slowed. Neither the amplitud e nor the kinetics of NMDA receptor-mediated EPSCs was significantly change d in the presence of 3 alpha5 betaS. The results of our experiments indicat e that neurosteroids affect NMDA receptors in motoneurons. The effect appea rs to be influenced by the receptor subunit composition.