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

Whole‐cell patch recordings were made from substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of 15‐ to 30‐day‐old rats. Endomorphin 1 (EM‐1) or EM‐2 (10 μM) hyperpolarized or induced an outward current in 26 of the 66 SG neurons. The I–V relationship showed that the peptide activates an inwardly rectifying K+ current. EM‐1 or EM‐2 (0.3–10 μM) 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. [Met5] enkephalin or [D‐Ala2, N‐Me‐Phe4, Gly5‐ol]‐enkephalin (DAMGO) (1–10 μM) 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. 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 μM) or bicuculline (10 μM). EM‐1 or DAMGO (1 or 5 μM) attenuated the glutamate‐evoked outward or biphasic currents in four of the seven SG neurons. EM‐1 (1 μM) reduced the frequency, but not the amplitude of miniature EPSCs or miniature IPSCs. Naloxone (1 μM) or the selective μ‐opioid receptor antagonist β‐funaltrexamine (β‐FNA, 25 μM) antagonized the action of EM; EM‐induced hyperpolarizations persisted in the presence of the κ‐opioid receptor antagonist (nor‐binaltorphimine dihydrochloride, 1 μM) and/or σ‐opioid receptor antagonist (naltrindole hydrochloride, 1 μM). It may be concluded that EM acting on μ‐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. British Journal of Pharmacology (2003) 140, 1088–1096. doi:10.1038/sj.bjp.0705534