Voltage-gated sodium channels are responsible not only for the fast upstroke of the action potential, 2 but they also modify cellular excitability via persistent and resurgent currents. Insecticides act via 3 permanently opening sodium channels to immobilize the animals. Cellular recordings performed 4 decades ago revealed distinctly hooked tail currents induced by these compounds. Here, we applied 5 the classical type-II pyrethroid deltamethrin on human cardiac Nav1.5 and observed resurgent-like 6 currents at very negative potentials in the absence of any pore-blocker, which resemble those hooked 7 tail currents. We show that deltamethrin dramatically slows both fast inactivation and deactivation of 8 Nav1.5 and thereby induces large persistent currents. Using the sea anemone toxin ATx-II as a tool to 9 prevent all inactivation-related processes, resurgent-like currents were eliminated while persistent 10 currents were preserved. Our experiments suggest that, in deltamethrin-modified channels, recovery 11 from inactivation occurs faster than delayed deactivation, opening a brief window for sodium influx 12 and leading to hooked, resurgent-like currents, in the absence of an open channel blocker. Thus, we 13 now explain with pharmacological methods the biophysical gating changes underlying the 14 deltamethrin induced hooked tail currents. 15

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