Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor
Takeda, M; Ikeda, M; Takahashi, M; Kanazawa, T; Nasu, M; Matsumoto, S
| HERO ID | 4371018 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor |
| Authors | Takeda, M; Ikeda, M; Takahashi, M; Kanazawa, T; Nasu, M; Matsumoto, S |
| Journal | Brain Research Bulletin |
| Volume | 98 |
| Page Numbers | 155-162 |
| Abstract | The aim of the present study was to investigate whether a GABAB receptor agonist could modulate ATP-activated neuronal excitability of nociceptive TRG neurons using perforated whole-cell patch-clamp and immunohistochemical techniques. Immunohistochemical analysis revealed that 86% of P2X3 receptor-immunoreactive, small-diameter TRG neurons co-expressed GABAB receptor. Under voltage-clamp conditions (Vh=-60mV), application of ATP activated the inward current in acutely isolated rat TRG neurons in a dose-dependent manner (10-50 μM) and this current could be blocked by pyridoxal-phosphate-6-azophenyl-27,47-disulfonic acid (PPADS) (10 μM), a selective P2 purinoreceptor antagonist. The peak amplitude of ATP-activated currents was significantly inhibited after application of GABAB receptor agonist, baclofen (10-50 μM), in a concentration-dependent and reversible manner. The baclofen-induced inhibition of ATP-activated current was abolished by co-application of 3-amino-2 (4-chlorophenyl)-2hydroxypropysufonic acid) saclofen, a GABAB receptor antagonist (50 μM). Under current-clamp conditions, application of 20 μM ATP significantly depolarized the membrane potential resulting in increased mean action potential frequencies, and these ATP-induced effects were significantly inhibited by baclofen and these effects were antagonized by co-application of saclofen. Together, the results suggested that GABAB receptor activation could inhibit the ATP-induced excitability of small-diameter TRG neurons activated through the P2X3 receptor. Thus, the interaction between P2X3 and GABAB receptors of small-diameter TRG neuronal cell bodies is a potential therapeutic target for the treatment of trigeminal nociception. |
| Doi | 10.1016/j.brainresbull.2013.08.005 |
| Pmid | 24004472 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |