Receptor sites for animal toxins targeting TRPV1 and VGICs. (A) The spider DkTx toxin latches onto the outer pore region of TRPV1 and stabilizes an open pore conformation. (B) Dc1a wedges into a cleft between the VSD and pore domains of Na_v and impedes VSD movement. (C) Charybodotoxin inserts a lysine side chain into the extracellular entrance to the selectivity filter of K_v and physically plugs the entryway of ion permeation. PDB accession nos. are as follows: TRPV1/DkTx (5IRX), NavPaS (6A90), and K_v2.1/charybodotoxin (4JTC).