Protein Kinases Mediate Enhancement Of Glycine-gated CT Channel Currents By 5-HT And NA In Rat Sacral Dorsal Commissural Neurons

It is well known that serotonin (5-HT) and noradrenaline (NA), which are present in descending inhibitory pathways, have antinociceptive effects, yet the mechanisms of their inhibitory actions are poorly understood Considerable evidence supports the idea that grycine (Gly) acts as a major inhibitory transmitter in spinal cord where glycine is likely to play an important role in modulating spinal nociceptive transmission, In the Gly-gated Cl" channel complexes, the binding of Gly to its receptors produces a large increase in Cl' conductance, followed by membrane hyperpolarization. Recently, it has become evident that phosphorylation of Gly receptors by intracellular second messenger-triggered protein kinases affects Gly receptor-mediated events. Since 5-HT and NA have been known to alter second messengers such as cAMP, DAG, IP₃ and Ca²⁺ in the target cells, the inhibitory effects of 5-HT and NA may result from the enhancement of inhibitory glycinergic transmission by Gly receptor phosphorylation mediated through the intracellular second messenger pathways. In this study, therefore, the effects of 5-HT and NA on Gly response were investigated in rat sacral dorsal commissural nucleus (SDCN) neurons. The SDCN represents the area just dorsal to the central canal of lower lumbar and sacral spinal cord. Our previous studies indicate that the SDCN is implicated in nociceptive transmission.The SDCN neurons were acutely dissociated from two-week-old Wistar rats. Electrical measurement were carried out by using nystatin perforated patch recording configuration under voltage-clamp condition at room temperature (22-25℃). Patch...