Nitric oxide inhibits GABA-evoked current in dorsal root ganglion neuron via PKG-dependent pathway

gamma -Aminobutyric acid (GABA) is considered a major inhibitory neurotrans mitter in the generation of presynaptic inhibition at central terminals of primary afferent fiber (PAF), while it has also been established that nitri c oxide (NO) may sensitize the terminals of nocisponsive PAFs and enhance n europeptide release, possibly via mechanisms involving the activation of a cyclic guanidine monophosphate (cGMP)-dependent PKG. The present work was u ndertaken to explore the modulatory effect of sodium nitroprusside (SNP), a donor of NO, on GABA-evoked current of isolated adult rat dorsal root gang lion (DRG) neurons and the intracellular mechanism involved, by means of wh ole-cell patch clamp recording. The results showed that 1 mM SNP reversibly inhibited the inward current evoked by 0.1 mM GABA (-1.05 +/- 0.17 nA vs. -0.63 +/- 0.11 nA, n = 22, p < 0.01 or 0.1 mM muscimol a specific GABAA rec eptor agonist (-1.70 +/- 0.39 nA vs. -1.01 +/- 0.24 nA, n = 6, p < 0.05), w hich could be cancelled by simultaneous application of 1 mM methylene blue, an inhibitor of PKG. After preapplication of SNP with increasing concentra tions 0.03, 0.1, 0.39 1, and 3 mM), SNP inhibited both 0.1 mM GABA-evoked c urrent (IC50 = 0.2423 mM, n = 5) and 0.1 mM muscimol-evoked current (IC50 = 0.3255 mM, n = 3) in DRG neurons in a dose-dependent manner. Therefore, it was suggested that PKG-dependent pathway may be involved in the NO-induced inhibition of GABAA receptor-mediated inward current in rat DRG neurons, w hich may be involved in the presynaptic disinhibition of nociceptive inform ation induced by NO under certain conditions. (C) 2001 Elsevier Science Inc .