Vertebrates can sense and avoid noxious heat that evokes pain. Many thermoTRP channels are associated with
temperature sensation. TRPV1 is a representative ion channel that is activated by noxious heat. Anoctamin 1 (ANO1) is a
Cl- channel activated by calcium that is highly expressed in small sensory neurons, colocalized with markers for
nociceptors, and most surprisingly, activated by noxious heat over 44°C. Although ANO1 is a Cl- channel, opening of this
channel leads to depolarization of sensory neurons, suggesting a role in nociception. Indeed, the functional deletion of
ANO1 in sensory neurons triggers the reduction in thermal pain sensation. Thus, it seems clear that ANO1 is a heat sensor
in a nociceptive pathway. Since ANO1 modulators are developed for the purpose of treating chronic diseases such as
cystic fibrosis, this finding is likely to predict unwanted effects and provide a guide for better developmental strategy.
Keywords: ANO1, CaCC, pain, heat, thermo TRP, sensory neurons.
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