Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae

Voltage-gated sodium channels are essential for the propagation of action potentials in nociceptive neurons. Na-v 1.7 is found in peripheral sensory and sympathetic neurons and involved in short-term and inflammatory pain. Na-v 1.8 and Na-v 1.3 are major players in nociception and neuropathic pain, respectively. In our effort to identify isoform-specific and high-affinity ligands for these channels, we investigated the effects of OD1, a scorpion toxin isolated from the venom of the scorpion Odonthobuthus doriae. Na-v 1.3, Na-v 1.7, and Na-v 1.8 channels were coexpressed with beta(1)-subunits in Xenopus laevis oocytes. Na+ currents were recorded with the two-electrode voltage-clamp technique. OD1 modulates Na-v 1.7 at low nanomolar concentrations: 1) fast inactivation is dramatically impaired, with an EC50 value of 4.5 nM; 2) OD1 substantially increases the peak current at all voltages; and 3) OD1 induces a substantial persistent current. Na-v 1.8 was not affected by concentrations up to 2 mu M, whereas Na-v 1.3 was sensitive only to concentrations higher than 100 nM. OD1 impairs the inactivation process of Na-v 1.3 with an EC50 value of 1127 nM. Finally, the effects of OD1 were compared with a classic alpha-toxin, AahII from Androctonus australis Hector and a classic alpha-like toxin, BmK M1 from Buthus martensii Karsch. At a concentration of 50 nM, both toxins affected Na-v 1.7. Na-v 1.3 was sensitive to AahII but not to BmK M1, whereas Na-v 1.8 was affected by neither toxin. In conclusion, the present study shows that the scorpion toxin OD1 is a potent modulator of Na-v 1.7, with a unique selectivity pattern.