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

doi:10.1038/nn.3111

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

Research output: Contribution to journal › Article › peer-review

304 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 language	English
Pages (from-to)	1015-1021
Number of pages	7
Journal	Nature Neuroscience
Volume	15
Issue number	7
DOIs	https://doi.org/10.1038/nn.3111
Publication status	Published - 2012 Jul

Bibliographical note

Funding Information:
This work was supported by the World Class University project (R31-2011-00101030), the Creative Research Initiatives Program (20120001246) and a grant (2011K000275) from the Brain Research Center of the 21st Century Frontier Research Program funded by of the Ministry of Education and Science and Technology and the National Research Foundation of the Republic of Korea.

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General Neuroscience

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

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.",

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

note = "Funding Information: This work was supported by the World Class University project (R31-2011-00101030), the Creative Research Initiatives Program (20120001246) and a grant (2011K000275) from the Brain Research Center of the 21st Century Frontier Research Program funded by of the Ministry of Education and Science and Technology and the National Research Foundation of the Republic of Korea.",

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AU - Wang, Fan

AU - Raouf, Ramin

AU - Wood, John N.

AU - Oh, Uhtaek

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

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