AI Article Synopsis
- Diarylamidines are small molecule drugs that inhibit certain ion channels, like glutamate receptors and DEG/ENaC/ASICs.
- Researchers identified a new ion channel called DiaaNaC from the brachiopod Novocrania anomala, which is activated by diarylamidines rather than traditional stimuli.
- The study explores the properties of DiaaNaC, including its activation by specific compounds like diminazene and the role of molecular alterations in its function.
Article 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 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).
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| http://dx.doi.org/10.1016/j.jbc.2024.108066 | DOI Listing |
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