ASIC2, also known as acid-sensing ion channel 2, is a mechanosensitive ion channel that plays crucial roles in various biological processes. It is involved in mechano-electrical transduction, interacts with other proteins in different pathways, and is associated with the regulation of multiple physiological functions. Genetic models, especially knockout (KO) mouse models, have been instrumental in understanding its functions [1,2,3,4,5,6].

In KO mouse models, deletion of Asic2 led to increased conditioned place preference to cocaine and morphine, indicating its role in drug-reinforced behavior [3]. Mice lacking both Asic2 and βENaC showed abolished pressure-induced constriction in renal afferent arterioles, along with mild renal injury and increased mean arterial blood pressure, suggesting their combined role in myogenic constriction [2]. Additionally, Asic2-deficient mice had impairments in muscle spindle responses to stretch and motor coordination tasks, and showed a specific effect on spinal alignment, demonstrating its role in proprioceptive sensing [6].

In conclusion, ASIC2 is a key player in processes such as mechano-electrical transduction, drug-reinforced behavior, myogenic constriction in renal vessels, and proprioceptive sensing. The use of Asic2 KO mouse models has significantly contributed to understanding its role in these biological processes and associated disease conditions like metabolic syndrome, renal injury, and drug-related behaviors [2,3,5].

References:

1. Yan, Xiaodong, Zhang, Sitao, Zhao, Haiyan, Wang, Wei, Zhang, Chen. 2021. ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors. In Neuroscience bulletin, 37, 1381-1396. doi:10.1007/s12264-021-00737-1. https://pubmed.ncbi.nlm.nih.gov/34215968/

2. Lu, Yan, Stec, David E, Liu, Ruisheng, Ryan, Michael, Drummond, Heather A. 2022. βENaC and ASIC2 associate in VSMCs to mediate pressure-induced constriction in the renal afferent arteriole. In American journal of physiology. Renal physiology, 322, F498-F511. doi:10.1152/ajprenal.00003.2022. https://pubmed.ncbi.nlm.nih.gov/35285274/

3. Fuller, Margaret J, Gupta, Subhash C, Fan, Rong, Radley, Jason J, Wemmie, John A. 2023. Investigating role of ASIC2 in synaptic and behavioral responses to drugs of abuse. In Frontiers in molecular biosciences, 10, 1118754. doi:10.3389/fmolb.2023.1118754. https://pubmed.ncbi.nlm.nih.gov/36793786/

4. Wang, Gang, Wang, Yu-Zhu, Yu, Yang, Wang, Jun-Jie. 2019. Inhibitory ASIC2-mediated calcineurin/NFAT against colorectal cancer by triterpenoids extracted from Rhus chinensis Mill. In Journal of ethnopharmacology, 235, 255-267. doi:10.1016/j.jep.2019.02.029. https://pubmed.ncbi.nlm.nih.gov/30772482/

5. Hamby, Madison, Stec, David E, Hildebrandt, Emily, Stec, Donald F, Drummond, Heather A. 2024. Mice lacking ASIC2 and βENaC are protected from high-fat-diet-induced metabolic syndrome. In Frontiers in endocrinology, 15, 1449344. doi:10.3389/fendo.2024.1449344. https://pubmed.ncbi.nlm.nih.gov/39224121/

6. Bornstein, Bavat, Watkins, Bridgette, Passini, Fabian S, Kröger, Stephan, Zelzer, Elazar. 2023. The mechanosensitive ion channel ASIC2 mediates both proprioceptive sensing and spinal alignment. In Experimental physiology, 109, 135-147. doi:10.1113/EP090776. https://pubmed.ncbi.nlm.nih.gov/36951012/