Interactions between animal toxins and Nav channels. (A; left) Side view of a Nav channel cartoon indicating the paddle motif (indicated in red) as the binding site for hanatoxin from the Grammostola rosea tarantula, Magi5 from the Hexathelidae spider Macrothele gigas, and BmK M1 from the Buthus martensii Karsch scorpion. (Middle) Structures of the three toxins colored according to residue class (green, hydrophobic; blue, positively charged; red, negatively charged; orange, polar). Toxin backbone is also shown. (Right) Effect of 100 nM hanatoxin (channel opening is inhibited), 1 µM Magi5 (channel opens at voltages where it is normally closed), and 100 nM BmK M1 (channel fast inactivation is inhibited) on rNav1.2a channels expressed in Xenopus laevis oocytes and recorded with the two-electrode voltage-clamp technique. Despite binding to a similar region on the Nav channel, each toxin has a different effect on channel opening or closing. Black trace represents control conditions, and red trace represents toxin. (B) Effect of 30 nM cone snail toxin GIIIA on rNav1.4-mediated currents recorded from Xenopus laevis oocytes. GIIIA blocks Na+ flow by binding to the outer region of the pore mouth. (C) Effect of 1 µM BTX, isolated from the poison dart frog, on rNav1.8 channels expressed in Xenopus laevis oocytes. BTX binds to the inner region of the pore to drastically modify Nav channel gating. Shown is the ability of BTX to open Nav channels at voltages where they are normally closed and to inhibit fast inactivation. Black trace represents control conditions, and red trace represents toxin.
