Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a

Martin Paukert, Xuanmao Chen, Georg Polleichtner, Hermann Schindelin, Stefan Gründer

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

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 Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)572-581
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number1
DOIs
StatePublished - Jan 4 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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