Acid-sensing ion channel 1 (ASIC1) is a proton-gated cation channel. It is activated in acidosis in both the central and peripheral nervous systems, participating in pain perception, synaptic plasticity, learning, memory, and various disease-related processes. It can detect extracellular acid fluctuations and increase membrane depolarization rates in response to acidic pH, conducting sodium and calcium ions across the membrane [3].

In atherosclerotic models, ASIC1 deficiency in ApoE-/-mice significantly attenuated atherogenesis. ASIC1 interacts with RIP1, promoting RIP1 phosphorylation at serine 166 and TFEB phosphorylation at serine 142, disrupting lipophagy and increasing lipid accumulation. Inhibition of this interaction restored TFEB-mediated lipophagy [1]. In pancreatic stellate cells (PSCs), ASIC1 knockdown weakened the enhanced proliferation and migration induced by pancreatic cancer cells, and also suppressed the increased phosphorylated ERK expression in PSCs [2]. In the development of chronic hypoxia-induced pulmonary hypertension, ASIC1 knockout (ASIC1-/-) mice exhibited diminished right ventricular systolic pressure, right ventricular hypertrophy, and arterial remodeling compared with wild-type mice [4].

In conclusion, ASIC1 plays crucial roles in multiple biological processes and disease conditions. Gene knockout mouse models, such as in atherosclerosis, pancreatic cancer, and pulmonary hypertension studies, have revealed that ASIC1 is involved in lipid metabolism, cell proliferation and migration, and vascular remodeling. These findings provide insights into the underlying mechanisms of related diseases and suggest that targeting ASIC1 could be a potential therapeutic strategy.

References:

1. Wang, Yuan-Mei, Tang, Huang, Tang, Ya-Jie, Feng, Yao-Guang, Gu, Hong-Feng. 2023. ASIC1/RIP1 accelerates atherosclerosis via disrupting lipophagy. In Journal of advanced research, 63, 195-206. doi:10.1016/j.jare.2023.11.004. https://pubmed.ncbi.nlm.nih.gov/37931656/

2. Zhu, Lei, Yin, Jianmei, Zheng, Fuhong, Yu, Yingqing, Liu, Haibo. 2020. ASIC1 inhibition impairs the proliferation and migration of pancreatic stellate cells induced by pancreatic cancer cells. In Neoplasma, 68, 174-179. doi:10.4149/neo_2020_200803N811. https://pubmed.ncbi.nlm.nih.gov/33516168/

3. Chauhan, Anurag Singh, Sahoo, Ganesh Chandra, Dikhit, Manas Ranjan, Das, Pradeep. . Acid-Sensing Ion Channels Structural Aspects, Pathophysiological Importance and Experimental Mutational Data Available Across Various Species to Target Human ASIC1. In Current drug targets, 20, 111-121. doi:10.2174/1389450119666180820103316. https://pubmed.ncbi.nlm.nih.gov/30124148/

4. Nitta, Carlos H, Osmond, David A, Herbert, Lindsay M, Walker, Benjimen R, Jernigan, Nikki L. 2013. Role of ASIC1 in the development of chronic hypoxia-induced pulmonary hypertension. In American journal of physiology. Heart and circulatory physiology, 306, H41-52. doi:10.1152/ajpheart.00269.2013. https://pubmed.ncbi.nlm.nih.gov/24186095/