Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes

Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):8430-8435. doi: 10.1073/pnas.1806614115. Epub 2018 Jul 30.


Acid-sensing ion channels (ASICs) are proton-gated ion channels broadly expressed in the vertebrate nervous system, converting decreased extracellular pH into excitatory sodium current. ASICs were previously thought to be a vertebrate-specific branch of the DEG/ENaC family, a broadly conserved but functionally diverse family of channels. Here, we provide phylogenetic and experimental evidence that ASICs are conserved throughout deuterostome animals, showing that ASICs evolved over 600 million years ago. We also provide evidence of ASIC expression in the central nervous system of the tunicate, Oikopleura dioica Furthermore, by comparing broadly related ASICs, we identify key molecular determinants of proton sensitivity and establish that proton sensitivity of the ASIC4 isoform was lost in the mammalian lineage. Taken together, these results suggest that contributions of ASICs to neuronal function may also be conserved broadly in numerous animal phyla.

Keywords: ASIC evolution; invertebrate; ligand recognition; nervous system; proton sensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / physiology*
  • Animals
  • Chordata / physiology*
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Mice
  • Phylogeny
  • Protein Isoforms


  • Acid Sensing Ion Channels
  • Protein Isoforms

Associated data

  • Dryad/10.5061/dryad.46320g1