GABAB receptors inhibit low-voltage activated and high-voltage activated Ca2+ channels in sensory neurons via distinct mechanisms

摘要: Growing evidence suggests that mammalian peripheral somatosensory neurons express functional receptors for gamma-aminobutyric acid, GABAA and GABAB. Moreover, local release of GABA by pain-sensing (nociceptive) nerve fibres has also been suggested. Yet, the significance receptor triggering in nociceptive is not fully understood. Here we used patch-clamp recordings from small-diameter cultured DRG to investigate effects GABAB agonist baclofen on voltage-gated Ca2+ currents. We found inhibited both low-voltage activated (LVA, T-type) high-voltage (HVA) currents a proportion 22% 32% respectively; were sensitive Gi/o inhibitor pertussis toxin. Inhibitory effect current types was about twice less efficacious as compared μ-opioid DAMGO. Surprisingly, only HVA but LVA modulation partially prevented G protein GDP-β-S. In contrast, reversed application reducing agent dithiothreitol (DTT). Inhibition T-type recovery such inhibition DTT successfully reconstituted expression system. Our data suggest mediated an unconventional signaling pathway involves redox mechanism. These findings reinforce idea targeting pain relief.