Department of Physiology, School of Medicine, Eulji University, Daejeon, Korea
The periaqueductal gray (PAG) is considered one of the important anatomical regions for pain modulation in the central nervous system (CNS). In acutely dissociated rat PAG neurons, the electrophysiological properties and action mechanisms of 5-HT1A agonist and μ-opioid agonist-induced activation of the inwardly rectifying K current using the nystatin-perforated patch-clamp recording modes under voltage-clamp conditions. Serotonin and D-Ala2,N-MePhe4,Gly5-ol-enkephalin (DAMGO)- induced activated inward K currents at a concentration-dependent manner. The postsynaptic serotonergic effect was mimicked by a specific 5-HT1A receptor agonist, 8-Hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT). These opioidergic and serotonergic activation of inward K current employed the similar intracellular mechanism of 4-aminopyridine (AP)-sensitive K channels via GTP-binding proteins (G-proteins). Co-application of 1μM DAMGO with 100 nM 8-OH-DPAT produced significant enhancement of inward K current. In conclusion, activation of postsynaptic μ-opioid and 5-HT1A receptors synergistically increased the inward K current. These results suggest a cellular mechanism within PAG for the analgesic effectiveness of combined therapies using opioids in conjuction with 5-HT1A. (Korean J Str Res 2007;15:9∼15)