Si Jun-qiang, Zhang Zhi-qin, Li Chun-xia, Wang Li-feng, Yang Yun-lei, Li Zhi-wang
Department of Physiology, Medical College Shihezi University, Shihezi 832002, China.
Acta Pharmacol Sin. 2004 May;25(5):623-9.
To explore the modulatory effect of substance P (SP) on GABA-activated current of dorsal root ganglion (DRG) neurons in rat.
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.
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.
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.
探讨P物质（SP）对大鼠背根神经节（DRG）神经元γ-氨基丁酸（GABA）激活电流的调节作用。
采用全细胞膜片钳技术记录从大鼠DRG神经元新鲜分离的神经元中SP和GABA激活的电流。通过快速溶液交换施加药物。
施加SP（28/41，68.5%）和GABA（36/41，88.2%）可在一些细胞中诱导浓度依赖性内向电流。SP（10 μmol/L）和GABA（100 μmol/L）激活的内向电流分别为（244±83）pA（n = 9）和（1.8±0.5）nA（n = 13）。大多数GABA激活电流有明显的三个过程，即峰值（I(p)）、稳态（I(ss)）和脱敏（I(d)）。GABA激活电流的脱敏是一个双相过程，包括快速和缓慢脱敏。然而，预先施加SP（0.001 - 1 μmol/L）可抑制GABA激活的内向电流，该电流被确定为GABAA受体介导的电流。抑制作用呈浓度依赖性。SP对GABA激活电流峰值的抑制作用大于对GABA激活电流稳态的抑制作用。SP（0.1 μmol/L）对GABA激活电流的抑制作用与施加SP后的时间有关，SP对GABA激活电流的抑制作用在约4分钟时达到峰值（49.8%±7.2%，n = 7，P < 0.01），约12分钟后完全恢复。用H - 7阻断蛋白激酶C（PKC）后重新进行膜片钳记录，SP对GABA激活电流的抑制作用几乎完全消除。
预先施加SP对GABA激活电流峰值的抑制作用比对GABA激活电流稳态的抑制作用更强。
