AIM: To explore the modulatory effect of substance P (SP) on GABA-activated current of dorsal root ganglion(DRG) neurons in rat. METHODS: The whole-cell patch-clamp technique was used to record SP- and GABA-activated currents in neurons freshly dissociated from rat DRG neurons. Drugs were applied by rapid solutionexchange. RESULTS: Application of SP (28/41, 68.5 %) and GABA (36/41, 88.2 %) could induce concentration-dependent inward current in some cells. SP-(10 mol/L) and GABA (100 mol/L)-activated inward currents were(24483) pA (n=9) and (1.80.5) nA (n=13), respectively. The majority of GABA-activated current had obviousthree processes, the peak value (Ip), the steady state (Iss) and the desensitization (Id). The desensitization of GABA-activated current was a biphasic process, including fast and slow desensitization. However, pre-application of SP(0.0011 mol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The inhibitory effects were concentration-dependent. The inhibitory effect of SP on the peakvalue of GABA-activated current was more than the steady state of GABA-activated current. The inhibition ofGABA-activated current by SP (0.1 mol/L) was related to the time after application of SP, the inhibition of GABA-activated currents by SP reached the peak at about 4 min (49.8 %7.2 %, n=7, P<0.01) and took about 12 min toget a full recovery. The inhibition of GABA-activated currents by SP was almost completely removed after block-ade of PKC by H-7 with the re-patch clamp. CONCLUSION: Pre-application of SP exerts a more strong inhibitoryeffect on the peak value of GABA-activated current than the steady state of GABA-activated current. AIM: To explore the modulatory effect of substance P (SP) on GABA-activated current of dorsal root ganglion (DRG) neurons in rat. METHODS: The whole-cell patch-clamp technique was used to record SP- and GABA-activated currents RESULTS: Application of SP (28/41, 68.5%) and GABA (36/41, 88.2%) could induce concentration-dependent inward current in some cells. The majority of GABA-G cells expressed GABA (100 mol / L) -activated intracellular currents (24483) pA (n = 9) and (1.80.5) nA activated current was obviousthree processes, the peak value (Ip), the steady state (Iss) and the desensitization (Id). The desensitization of GABA-activated current was a biphasic process, including fast and slow desensitization. However, pre-application of SP (0.0011 mol / L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The in The inhibitory effect of SP on the peak value of GABA-activated current was more than the steady state of GABA-activated current. The inhibition of GABA-activated current by SP (0.1 mol / L) was related to the time after application of SP, the inhibition of GABA-activated currents by SP reached the peak at about 4 min (49.8% 7.2%, n = 7, P <0.01) and took about 12 min toget a full recovery. The inhibition of GABA -activated currents by SP was almost completely removed after block-address of PKC by H-7 with the re-patch clamp. CONCLUSION: Pre-application of SP exerts a more strong inhibitory effect on the peak value of GABA-activated current than the steady state of GABA-activated current.