Effects of endomorphin on substantia gelatinosa neurons in rat spinal cord slices

1 Whole-cell patch recordings were made from substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of 15- to 30-day-old rats. 2 Endomorphin 1 (EM-1) or EM-2 (less than or equal to 10 muM) hyperpolarized or induced all outward current in 26 of the 66 SG neurons. The I-V relationship showed that the peptide activates an inwardly rectifying K+ current. 3 EM-1 or EM-2 (0.3-10 muM) suppressed short-latency excitatory postsynaptic currents (EPSCs) and long-latency inhibitory postsynaptic currents (IPSCs) in nearly all SG neurons tested or short-latency IPSCs in six of the 10 SG neurons. [Met(5)] enkephalin or [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) (1-10 muM) depressed EPSCs and IPSCs. EM-1 or EM-2 depressed synaptic responses without causing a significant change in holding currents or inward currents induced by glutamate. 4 Glutamate also evoked a short-latency outward current in five SG neurons or a biphasic current in two neurons; the outward current was blocked by tetrodotoxin (TTX, 0.3 muM) or bicuculline (10 muM). EM-1 or DAMGO (1 or 5 muM) attenuated the glutamate-evoked outward or biphasic currents in four of the seven SG neurons. 5 EM-1 (1 muM) reduced the frequency, but not the amplitude of miniature EPSCs or miniature IPSCS. 6 Naloxone (1 muM) or the selective mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA, 25 muM) antagonized the action of EM; EM-induced hyperpolarizations persisted in the presence of the kappa-opioid receptor antagonist (nor-binaltorphimine dihydrochloride, 1 muM) and/or sigma-opioid receptor antagonist (naltrindole hydrochloride, 1 muM). 7 It may be concluded that EM acting on it-opioid receptors hyperpolarizes a population of SG neurons by activating an inwardly rectifying K+ current, and attenuates excitatory and inhibitory synaptic currents evoked in a population of SG neurons, probably by a presynaptic site of action.