Modulatory effect of substance P on GABA-activated currents from rat dorsal root ganglion

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 solution exchange. 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 μmol/L) and GABA (100 μmol/L)-activated inward currents were (244±83) pA (n=9) and (1.8±0.5) nA (n=13), respectively. The majority of GABA-activated current had obvious three processes, the peak value (I_p), the steady state (I_ss) and the desensitization (I_d). The desensitization of GABA-activated current was a biphasic process, including fast and slow desensitization. However, pre-application of SP (0.001-1 μmol/L) could inhibit the GABA-activated inward current which was identified to be GABA_A receptor-mediated current. The inhibitory effects were concentration-dependent. 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 μmol/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 to get a full recovery. The inhibition of GABA-activated currents by SP was almost completely removed after blockade 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.