1. Diarylamidine activation of a brachiopod DEG/ENaC/ASIC channel.
- Author
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Martí-Solans, Josep, Børve, Aina, Hejnol, Andreas, and Lynagh, Timothy
- Subjects
- *
SODIUM channels , *SITE-specific mutagenesis , *GLUTAMATE receptors , *BRACHIOPODA , *SODIUM ions , *ION channels , *LIGAND-gated ion channels - Abstract
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/acid-sensing ion channels. Here, we discover a degenerin/epithelial sodium channel/acid-sensing ion 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, 40,6-diamidino-2-phenylindole, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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