PT  - JOURNAL ARTICLE
AU  - Martí-Solans, Josep
AU  - Børve, Aina
AU  - Hejnol, Andreas
AU  - Lynagh, Timothy
TI  - Diarylamidine activation of a brachiopod DEG/ENaC/ASIC channel
AID  - 10.1101/2024.08.26.609674
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.08.26.609674
4099  - http://biorxiv.org/content/early/2024/08/26/2024.08.26.609674.short
4100  - http://biorxiv.org/content/early/2024/08/26/2024.08.26.609674.full
AB  - Diarylamidines are a group of widely used small molecule drugs. One common use of diarylamidines is their pharmacological inhibition of ligand-gated cation channels, including tetrameric ionotropic glutamate receptors and trimeric degenerin/epithelial sodium channel channel/acid-sensing ion channels (DEG/ENaC/ASICs). Here, we discover a DEG/ENaC/ASIC channel from the brachiopod (lamp shell) Novocrania anomala, at which diarylamidines act as agonists. The channel is closely related to bile acid-gated, pH-gated, and peptide-gated channels but is not activated by such stimuli. We describe activation of the channel by diminazene, DAPI, and pentamidine, examine several biophysical and pharmacological properties, and briefly explore the molecular determinants of channel activity with site-directed mutagenesis. We term this channel the diarylamidine-activated sodium channel (DiaaNaC).Competing Interest StatementThe authors have declared no competing interest.