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Glycine and GABA A receptor‐mediated synaptic transmission in rat substantia gelatinosa: inhibition by μ‐opioid and GABA B agonists
Author(s) -
Grudt Timothy J.,
Henderson Graeme
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.473bt.x
Subject(s) - damgo , strychnine , bicuculline , chemistry , gabaa receptor , agonist , glycine receptor , inhibitory postsynaptic potential , pharmacology , neuroscience , receptor , opioid receptor , glycine , biochemistry , amino acid , biology
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 μ m ) but was insensitive to bicuculline (10 μ m ), TTX (0.5 μ m ), [D‐Ala 2 , N ‐Me‐Phe 4 , Gly 5 ‐ol]‐enkephalin (DAMGO, 1 μ m ) or baclofen (30 μ m ). The single‐channel conductance underlying the noise was estimated to be 21 pS. 4 The μ‐opioid agonist DAMGO (1‐10 μ m ) reduced the amplitude of the evoked glycine receptor‐mediated IPSC and the evoked GABA A receptor‐mediated IPSC. The μ‐opioid antagonist D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Thr‐Pen‐Thr‐NH 2 (CTAP, 1 μ m ) reversed the DAMGO inhibition. 5 The GABA B agonist baclofen (30 μ 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)‐ hydroxypropyl‐P‐benzyl‐phosphinic acid (CGP 55845A, 1 μ m ). 6 Both DAMGO and baclofen reduced the frequency of glycine and GABA A receptor‐mediated mIPSCs 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.