Conservation and divergence in NaChBac and Na_V1.7 pharmacology reveals novel drug interaction mechanisms.

ABSTRACT: Voltage-gated Na⁺ (Na_V) channels regulate homeostasis in bacteria and control membrane electrical excitability in mammals. Compared to their mammalian counterparts, bacterial Na_V channels possess a simpler, fourfold symmetric structure and have facilitated studies of the structural basis of channel gating. However, the pharmacology of bacterial Na_V remains largely unexplored. Here we systematically screened 39 Na_V modulators on a bacterial channel (NaChBac) and characterized a selection of compounds on NaChBac and a mammalian channel (human Na_V1.7). We found that while many compounds interact with both channels, they exhibit distinct functional effects. For example, the local anesthetics ambroxol and lidocaine block both Na<

SUBMITTER: Zhu W 

PROVIDER: S-EPMC7329812 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature