Li Shao, An Jie, Sun Chang-Kai, Li Zhi-Wang
Department of Physiology and Research Center of Brain Disorders, Dalian Medical University, Dalian 116027, China.
Sheng Li Xue Bao. 2004 Jun 25;56(3):384-8.
By means of whole-cell patch clamp technique, the modulatory effect of caffeine on GABA-activated currents (I(GABA)) was investigated in acutely isolated rat dorsal root ganglion (DRG) neurons. The majority of the neurons examined (113/116) were sensitive to GABA (11000 micromol/L). GABA activated a concentration-dependent inward current, which manifested obvious desensitization. In 58 out of 108 neurons, caffeine induced a small inward current, while in others no detectable current was observed. After the neurons were treated with caffeine (0.1100 micromol/L) prior to the application of GABA (100 micromol/L) for 30 s, GABA-activated inward currents were obviously inhibited. Caffeine shifted the GABA dose-response curve downward and decreased the maximum response to 57% without changing K(d) value. These results indicate that the inhibitory effect is non-competitive. The pretreatment with caffeine (10 micromol/L) inhibited I(GABA) which was potentiated by diazepam (1 micromol/L). Intracellular application of H-8 almost completely abolished the inhibitory effect of caffeine on I(GABA). Because GABA can induce primary afferent depolarization (PAD), our results suggest that caffeine may be able to antagonize the effect of presynaptic inhibition of GABA in primary afferent.
采用全细胞膜片钳技术，在急性分离的大鼠背根神经节（DRG）神经元中研究了咖啡因对γ-氨基丁酸（GABA）激活电流（I(GABA)）的调制作用。大多数被检测的神经元（113/116）对GABA（11000微摩尔/升）敏感。GABA激活了一种浓度依赖性内向电流，该电流表现出明显的脱敏现象。在108个神经元中的58个中，咖啡因诱发了一个小的内向电流，而在其他神经元中未观察到可检测到的电流。在用GABA（100微摩尔/升）施加前30秒用咖啡因（0.1100微摩尔/升）处理神经元后，GABA激活的内向电流明显受到抑制。咖啡因使GABA剂量反应曲线向下移动，并使最大反应降低至57%，而不改变解离常数（K(d)）值。这些结果表明这种抑制作用是非竞争性的。用咖啡因（10微摩尔/升）预处理可抑制I(GABA)，而地西泮（1微摩尔/升）可增强该电流。细胞内应用H-8几乎完全消除了咖啡因对I(GABA)的抑制作用。由于GABA可诱导初级传入去极化（PAD），我们的结果表明咖啡因可能能够拮抗初级传入中GABA的突触前抑制作用。
