期刊
NATURE NEUROSCIENCE
卷 15, 期 7, 页码 1015-1021出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3111
关键词
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资金
- World Class University [R31-2011-00101030]
- Creative Research Initiatives Program [20120001246]
- Brain Research Center [2011K000275]
- Ministry of Education and Science and Technology
- National Research Foundation of the Republic of Korea
- National Research Foundation of Korea [R31-2012-000-10103-0, 22-2009-00-008-00] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Biotechnology and Biological Sciences Research Council [BB/F000227/1] Funding Source: researchfish
- Medical Research Council [G0901905] Funding Source: researchfish
- BBSRC [BB/F000227/1] Funding Source: UKRI
- MRC [G0901905] Funding Source: UKRI
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 Ca2+-activated chloride channel that is essential for numerous physiological functions. We found that ANO1 was activated by temperatures over 44 degrees 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.
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