Glycine and GABAA receptor-mediated synaptic transmission in rat substantia gelatinosa:: inhibition by μ-opioid and GABAB agonists

1. Bicuculline-sensitive and strychnine-sensitive inhibitory postsynaptic currents (IPSCs) could be evoked in neurones of the rat substantia gelatinosa of the spinal trigeminal nucleus pars caudalis. 2. Spontaneous tetrodotoxin (TTX)-insensitive-mediated miniature IPSCs (mIPSCs) blocked by strychnine or bicuculline were also present in many neurones. The decay of the glycine receptor-mediated mIPSCs was fitted by a single exponential, whereas the decay of the GABA(A) receptor-mediated mIPSCs could in some instances be fitted by a single exponential, but in other instances required two exponentials. 3. An increase in baseline current noise developed during the course of the recording. This noise was abolished by strychnine (1 mu M) but was insensitive to bicuculline (10 mu M), TTX (0.5 mu M), [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO, 1 mu M) or baclofen (30 mu M). The single-channel conductance underlying the noise was estimated to be 21 pS. 4. The mu-opioid agonist DAMGO (1-10 mu M) reduced the amplitude of the evoked glycine receptor-mediated IPSC and the evoked GABA(A) receptor-mediated IPSC. The mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP, 1 mu M) reversed the DAMGO inhibition. 5. The GABA(B) agonist baclofen (30 mu M) reduced the amplitude of the evoked glycine receptor-mediated IPSC and the GABA(A) receptor-mediated IPSC. The inhibition was reversed by the selective GABA(B) antagonist 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxgpropyl-P-benzyl-phosphinic acid (CGP 55846A, 1 mu M). 6. Both DAMGO and baclofen reduced the frequency of glycine and GABA(A) receptor-mediated mIPSC's without affecting average amplitude, and increased the percentage of failures of the evoked glycine and GABA(A) receptor-mediated IPSCs, suggesting a presynaptic site of action.