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Updated: May 22, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons
Hawon Cho1, Young Duk Yang, Jesun Lee
1Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
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.
Insights
Anoctamin 1 (ANO1) acts as a heat sensor in sensory neurons, detecting painful heat stimuli. Its role in nociception was confirmed by reduced pain behaviors in models lacking ANO1.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Nociceptors are primary afferent neurons detecting harmful stimuli.
- Anoctamin 1 (ANO1/TMEM16A) is a calcium-activated chloride channel involved in physiological functions.
- The specific role of ANO1 in thermal nociception remains largely unexplored.
Purpose of the Study:
- To investigate the role of Anoctamin 1 (ANO1) in the detection of noxious heat stimuli.
- To determine if ANO1 functions as a heat sensor in nociceptors.
Main Methods:
- Examined ANO1 activation by heat in vitro.
- Assessed ANO1 expression and localization in dorsal root ganglion (DRG) neurons.
- Utilized heat ramp stimulation on DRG neurons.
- Investigated the effects of ANO1 knockdown and deletion on thermal pain behaviors in vivo.
Main Results:
- ANO1 is activated by temperatures exceeding 44°C with high heat sensitivity.
- ANO1 is expressed in small sensory neurons and colocalizes with nociceptor markers.
- Heat ramps induced robust ANO1-dependent depolarization in DRG neurons.
- ANO1 knockdown or deletion significantly reduced nociceptive behavior in thermal pain models.
Conclusions:
- ANO1 functions as a heat sensor in sensory neurons.
- ANO1 plays a critical role in detecting and mediating nociceptive thermal stimuli.
- ANO1 is a potential therapeutic target for managing thermal pain.
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