The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention

In the nervous system, a decrease in extracellular pH is a common feature of various physiological and pathological processes, includ- ing 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 iden- tification of ASlCs as critical acid-sensing extracellular proton receptors, growing evidence has suggested that the activation of ASlCs plays important roles in physiological processes such as nociception, mechanosensation, synaptic plasticity, learning and memory. However, the over-activation of ASlCs is also linked to adverse outcomes for certain pathological processes, such as brain ischemia and multiple sclerosis. Based on the well-demonstrated role of ASlCla activation in acidosis-mediated brain injury, small molecule inhibitors of ASlCla may represent novel therapeutic agents for the treatment of neurological disorders, such as stroke.