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 micromol/L) and GABA (100 micromol/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 micromol/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 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 micromol/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.