[Inhibitory effect of caffeine on GABA-activated current in acutely isolated rat dorsal root ganglion neurons].
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 (1~1000 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 (0.1~100 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.
Li
Shao
S
Department of Physiology and Research Center of Brain Disorders, Dalian Medical University, Dalian 116027, China.
An
Jie
J
Sun
Chang-Kai
CK
Li
Zhi-Wang
ZW
D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D002110:Caffeine; D005680:gamma-Aminobutyric Acid