Modulation of glycine-activated chloride currents by substance P in rat sacral dorsal commissural neurons

The modulatory effect of substance P (SP) on strychnine-sensitive glycine (Gly) response was examined in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using nystatin perforated patch recording configuration under voltage-clamp conditions. Application of SP potentiated 30 mumol/L Gly-activated chloride current (IGly) in a concentration-dependent manner over the range of 1 nmol/L to 1 mumol/L at a holding potential of -40 mV. SP neither changed the reversal potential of Gly response nor affected the affinity of Gly to its receptor. The SP potentiation effect could be blocked by spantide as well as a selective NK1 receptor antagonist, L-668, 169, but not by NK2 receptor antagonist, L-659, 877. The facilitatory action of SP on IGly could also be abolished by pretreatment with chelerythrine or KN-62 in different neurons, a finding suggesting that protein kinase C (PKC) or Ca2+/calmodulin-dependent protein kinase II (CaMK II) possibly contributes to an intracellular pathway of SP in the augmentation of IGly. The results imply that SP may suppress nociception in the spinal cord by potentiating Gly response.