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Pain, Itch and Their Disorders

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Enhancement of TRPV1-mediated nociception by anoctamin 1 activation

  • P2-179
  • 高山 靖規 / Yasunori Takayama:1 歌 大介 / Daisuke Uta:2,3 古江 秀昌 / Hidemasa Furue:2,4 富永 真琴 / Makoto Tominaga:1,4 
  • 1:岡崎統合バイオサイエンスセンター・細胞生理 / Div Cell Signaling, OIIB, Aichi, Japan 2:生理学研究所・神経シグナル / Div Neural Signaling, NIPS, Aichi, Japan 3:富山大学・応用薬理学教室 / Dept Applied Pharmacol, Univ of Toyama, Toyama, Japan 4:総合研究大学院大学・生理科学専攻 / Dept Physiol, SOKENDAI, Kanagawa, Japan 

Transient receptor potential (TRP) V4 channels have been reported to interact with a calcium-activated chloride channel, anoctamin 1 (ANO1) in choroid plexus epithelial cells in which calcium entering the cells through TRPV4 activates ANO1. The concept prompted us to pursue another example in sensory neurons. In this study, we focused on TRPV1 with high calcium permeability. About 75% of TRPV1-expressing dorsal root ganglia (DRG) neurons also expressed ANO1. We hypothesized that ANO1 activation induces pain-enhancement in the physiological condition in DRG neurons because activation of chloride channels induces depolarization in DRG neurons due to high intracellular chloride concentrations. As expected, capsaicin-activated currents were significantly larger in HEK293 cells expressing both TRPV1 and ANO1 than in the cells expressing TRPV1 or ANO1 alone. Similar results were obtained in the isolated DRG neurons. An ANO1 blocker, T16Ainh-A01 (A01), reduced the capsaicin-activated currents by half in DRG neurons. Furthermore, concomitant application of A01 reduced the capsaicin-induced facilitation of spontaneous excitatory synaptic transmission in the superficial spinal dorsal horn of mice. These findings suggest that TRPV1-mediated nociception could be inhibited by ANO1 blockade. Indeed, pain-related behaviors in mice treated with capsaicin and A01 were significantly reduced compared with mice given capsaicin alone. These results indicate that TRPV1-ANO1 interaction is a pain-enhancing mechanism in the peripheral nervous system.

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