- 作者: Yuan-Ren Cheng, Bo-Yang Jiang and Chih-Cheng Chen
- 作者服務機構: 1. Department of Life Science, National Taiwan University, Taipei 106, Taiwan 2. Institute of Biomedical Sciences, Academia Sinica, 128, Academia Rd. Sec. 2, Taipei 115, Taiwan 3. Taiwan Mouse Clinic – National Comprehensive Mouse Phenotyping and Drug Testing Center, Academia Sinica, 128, Academia Rd. Sec. 2, Taipei 115, Taiwan
- 中文摘要:
- 英文摘要:
Background
Acid-sensing ion channels (ASICs) are a group of amiloride-sensitive ligand-gated ion channels belonging to the family of degenerin/epithelial sodium channels. ASICs are predominantly expressed in both the peripheral and central nervous system and have been characterized as potent proton sensors to detect extracellular acidification in the periphery and brain.
Main body
Here we review the recent studies focusing on the physiological roles of ASICs in the nervous system. As the major acid-sensing membrane proteins in the nervous system, ASICs detect tissue acidosis occurring at tissue injury, inflammation, ischemia, stroke, and tumors as well as fatiguing muscle to activate pain-sensing nerves in the periphery and transmit pain signals to the brain. Arachidonic acid and lysophosphocholine have been identified as endogenous non-proton ligands activating ASICs in a neutral pH environment. On the other hand, ASICs are found involved in the tether model mechanotransduction, in which the extracellular matrix and cytoplasmic cytoskeletons act like a gating-spring to tether the mechanically activated ion channels and thus transmit the stimulus force to the channels. Accordingly, accumulating evidence has shown ASICs play important roles in mechanotransduction of proprioceptors, mechanoreceptors and nociceptors to monitor the homoeostatic status of muscle contraction, blood volume, and blood pressure as well as pain stimuli.
Conclusion
Together, ASICs are dual-function proteins for both chemosensation and mechanosensation involved in monitoring physiological homoeostasis and pathological signals. - 中文關鍵字:
- 英文關鍵字: ASIC, ASIC3, Mechanotransduction, Nociceptor, Pain, Proprioception