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The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons
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The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons
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Journal Article
The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons
2012
Overview
This study reports that the Ca
2+
-activated chloride channel anoctamin 1 (ANO1) is activated by heat and is expressed in mouse dorsal root ganglion neurons.
Ano1
deletion leads to a deficit in thermal nociception, suggesting that this channel acts as a new heat sensor in pain pathways.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
