The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons.
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.
Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Hawon
H
Cho
Young Duk
YD
Yang
Jesun
J
Lee
Byeongjoon
B
Lee
Tahnbee
T
Kim
Yongwoo
Y
Jang
Seung Keun
SK
Back
Heung Sik
HS
Na
Brian D
BD
Harfe
Fan
F
Wang
Ramin
R
Raouf
John N
JN
Wood
Uhtaek
U
Oh
D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000172:deficiency / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009619:Nociceptors / Q000378:metabolism* / Q000502:physiology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D065101:Chloride Channel Agonists; D018118:Chloride Channels; D002118:Calcium