Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels

被引:206
作者
Bautista, Diana M. [1 ,2 ]
Sigal, Yaron M. [1 ,2 ]
Milstein, Aaron D.
Garrison, Jennifer L.
Zorn, Julie A.
Tsuruda, Pamela R. [1 ,2 ]
Nicoll, Roger A. [1 ,2 ]
Julius, David [1 ,2 ]
机构
[1] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA
关键词
D O I
10.1038/nn.2143
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In traditional folk medicine, Xanthoxylum plants are referred to as 'toothache trees' because their anesthetic or counter-irritant properties render them useful in the treatment of pain. Psychophysical studies have identified hydroxy-alpha-sanshool as the compound most responsible for the unique tingling and buzzing sensations produced by Szechuan peppercorns or other Xanthoxylum preparations. Although it is generally agreed that sanshool elicits its effects by activating somatosensory neurons, the underlying cellular and molecular mechanisms remain a matter of debate. Here we show that hydroxy-alpha-sanshool excites two types of sensory neurons, including small-diameter unmyelinated cells that respond to capsaicin (but not mustard oil) as well as large-diameter myelinated neurons that express the neurotrophin receptor TrkC. We found that hydroxy-alpha-sanshool excites neurons through a unique mechanism involving inhibition of pH-and anesthetic-sensitive two-pore potassium channels (KCNK3, KCNK9 and KCNK18), providing a framework for understanding the unique and complex psychophysical sensations associated with the Szechuan pepper experience.
引用
收藏
页码:772 / 779
页数:8
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