Acid-Sensing Ion Channels (ASICs) and pH in Synapse Physiology

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Although brain pH is tightly controlled, it can be more dynamic than commonly appreciated. Physiological fluctuations in extracellular pH provide ample opportunity for protons to influence synaptic signaling. A number of synaptic proteins are modified by extracellular pH. Of these, the acid sensing ion channels (ASICs) are gated by extracellular protons and thus they may be particularly well suited to respond to synaptic pH. Here we review extracellular pH changes that accompany neural activity, the synaptic localization of ASICs, and their known effects on synapse function. Results from manipulating ASICs in mice suggest important roles for synaptic ASICs in behavior and neurological disease.