A novel spider toxin as a selective antagonist of the Kv1 subfamily of voltage-gated potassium channels through gating modulation.

ABSTRACT: Members of the voltage-gated potassium channel subfamily (Kv1) are essential for the nervous and immune systems, necessitating novel modulators and deeper insights into their structure-function relationships. While all known peptide inhibitors targeting Kv1 channels are pore blockers, we identified MrVIII (κ-HxTx-MrVIII), a novel peptide toxin from the venom of spider Macrothele raveni, as the first voltage-gating modifier antagonist with selective activity against Kv1 channels. MrVIII exhibits high-affinity inhibition of Kv1.2, Kv1.3, Kv1.5, and Kv1.6, completely suppressing their currents. By contrast, it selectively inhibits the initial activation phase of Kv1.1, Kv1.4, and Kv1.7 with lower affinity, reflecting its differential subtype modulation. Gating current analyses revealed that M

SUBMITTER: Xiao Z 

PROVIDER: S-EPMC11984586 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature