Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H+. H+ is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H+ could in principle gate a channel by titration of a single amino acid. Experimental evidence suggests a more complex situation, however. For example, it has been shown that extracellular Ca2+ ions compete with H+; probably Ca2+ ions bound to the extracellular loop of ASICs stabilize the closed state of the channel and have to be displaced before the channel can open. In such a scheme, amino acids contributing to Ca2+ binding would also be candidates contributing to H+ gating. In this study we systematically screened more than 40 conserved, charged amino acids in the extracellular region of ASIC1a for a possible contribution to H+ gating. We identified four amino acids where substitution strongly affects H+ gating: Glu63, His72/His73, and Asp78. These amino acids are highly conserved among H+-sensitive ASICs and are candidates for the “H+ sensor” of ASICs.


Molecular, Cellular and Biomedical Sciences

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Journal of Biological Chemistry


American Society for Biochemistry and Molecular Biology

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© 2008 by The American Society for Biochemistry and Molecular Biology, Inc


This research was originally published in The Journal of biological chemistry. Paukert M, Chen X, Polleichtner G, Schindelin H, Grunder S. Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a. 2008;283(1):572-81. © the American Society for Biochemistry and Molecular Biology.