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


CONCLUSIONS
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.
Si
Jun-qiang
JQ
Department of Physiology, Medical College Shihezi University, Shihezi 832002, China. sijunqiang11@hotmail.com
Zhang
Zhi-qin
ZQ
Li
Chun-xia
CX
Wang
Li-feng
LF
Yang
Yun-lei
YL
Li
Zhi-wang
ZW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D013373:Substance P; D005680:gamma-Aminobutyric Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C