Abstract

Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na⁺ channel inactivation without modifying activation process. Here we report that β-PMTX modifies rat brain type II Na⁺ channel α-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart α-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na⁺ channels and compared modification of the steady-state Na⁺ currents by β-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of β-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na⁺channels.