Acid-sensing ion channels (ASICs) are ligand-gated ion channels that are exquisitely sensitive to extracellular protons and can sense transient as well as sustained acidification. In this review, we will discuss activation and desensitization of ASICs by protons. We show that a linear reaction scheme can reproduce the basic electrophysiological properties of ASICs, including steady-state desensitization. Moreover, we will discuss how a desensitizing receptor can sense sustained acidosis and what we know about the putative proton sensor. We will briefly discuss modulation of proton gating by neuropeptides and small positively charged ligands. Finally, we will review the pore properties of ASICs and their relation to the recently reported crystal structure of the open ASIC pore. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.
Keywords: Desensitization; ENaC; Gating; Ion pore; Proton; pH.
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