Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Acta Pharmacol Sin. 2013 Jan;34(1):33-8. doi: 10.1038/aps.2012.81. Epub 2012 Jul 23.
In the nervous system, a decrease in extracellular pH is a common feature of various physiological and pathological processes, including synaptic transmission, cerebral ischemia, epilepsy, brain trauma, and tissue inflammation. Acid-sensing ion channels (ASICs) are proton-gated cation channels that are distributed throughout the central and peripheral nervous systems. Following the recent identification of ASICs as critical acid-sensing extracellular proton receptors, growing evidence has suggested that the activation of ASICs plays important roles in physiological processes such as nociception, mechanosensation, synaptic plasticity, learning and memory. However, the over-activation of ASICs is also linked to adverse outcomes for certain pathological processes, such as brain ischemia and multiple sclerosis. Based on the well-demonstrated role of ASIC1a activation in acidosis-mediated brain injury, small molecule inhibitors of ASIC1a may represent novel therapeutic agents for the treatment of neurological disorders, such as stroke.
在神经系统中，细胞外 pH 值降低是各种生理和病理过程的共同特征，包括突触传递、脑缺血、癫痫、脑外伤和组织炎症。酸感应离子通道（ASICs）是质子门控阳离子通道，分布于中枢和外周神经系统。最近发现 ASICs 是关键的酸感应细胞外质子受体，越来越多的证据表明 ASICs 的激活在痛觉、机械感觉、突触可塑性、学习和记忆等生理过程中发挥重要作用。然而，ASICs 的过度激活也与某些病理过程的不良后果有关，如脑缺血和多发性硬化症。鉴于 ASIC1a 激活在酸中毒介导的脑损伤中的作用得到了充分证实，ASIC1a 的小分子抑制剂可能成为治疗中风等神经疾病的新型治疗药物。
