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Changes of extracellular pH values can have profound effects on neuronal function.For example,the low pH (also called acidosis) generated in brain ischemia causes acute cell injury by depolarizing neurons.For years the receptors that detect pH variations surrounding neurons and their physiological/pathological importance remain uncertain.The recent finding that acidosis activates a distinct family of membrane ion channels,the acid-sensing ion channels (ASICs) in both peripheral and central neurons has dramatically changed the view of acidosis-associated signaling and provided a new strategy for therapeutic inventions.Although proton is the only known agonist for the activation of ASICs,a variety of extracellular and intracellular signaling molecules can modulate the activities of ASICs and have profound influence on the functions of these channels in both physiological and pathological processes.