The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons

Hawon Cho, Young Duk Yang, Jesun Lee, Byeongjoon Lee, Tahnbee Kim, Yongwoo Jang, Seung Keun Back, Heung Sik Na, Brian D. Harfe, Fan Wang, Ramin Raouf, John N. Wood, Uhtaek Oh

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203 Citations (Scopus)

Abstract

Nociceptors are a subset of small primary afferent neurons that respond to noxious chemical, thermal and mechanical stimuli. Ion channels in nociceptors respond differently to noxious stimuli and generate electrical signals in different ways. Anoctamin 1 (ANO1 also known as TMEM16A) is a Ca 2+-activated chloride channel that is essential for numerous physiological functions. We found that ANO1 was activated by temperatures over 44 °C with steep heat sensitivity. ANO1 was expressed in small sensory neurons and was highly colocalized with nociceptor markers, which suggests that it may be involved in nociception. Application of heat ramps to dorsal root ganglion (DRG) neurons elicited robust ANO1-dependent depolarization. Furthermore, knockdown or deletion of ANO1 in DRG neurons substantially reduced nociceptive behavior in thermal pain models. These results indicate that ANO1 is a heat sensor that detects nociceptive thermal stimuli in sensory neurons and possibly mediates nociception.

Original languageEnglish
Pages (from-to)1015-1021
Number of pages7
JournalNature Neuroscience
Volume15
Issue number7
DOIs
Publication statusPublished - 2012 Jul

ASJC Scopus subject areas

  • Neuroscience(all)

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    Cho, H., Yang, Y. D., Lee, J., Lee, B., Kim, T., Jang, Y., Back, S. K., Na, H. S., Harfe, B. D., Wang, F., Raouf, R., Wood, J. N., & Oh, U. (2012). The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nature Neuroscience, 15(7), 1015-1021. https://doi.org/10.1038/nn.3111