Potent Modulation of the Voltage-Gated Sodium Channel Nav1.7 by OD1, a Toxin from the Scorpion Odonthobuthus doriae

• Published in: Molecular pharmacology 2006-07, Vol.70 (1), p.405
• Main Authors: Maertens, Chantal, Cuypers, Eva, Amininasab, Mehriar, Jalali, Amir, Vatanpour, Hossein, Tytgat, Jan
• Format: Article
• Language: English
• Subjects: Animals; Dose-Response Relationship, Drug; Female; Insect Proteins - pharmacology; Ion Channel Gating - drug effects; Membrane Potentials - drug effects; Oocytes - drug effects; Oocytes - metabolism; Oocytes - physiology; Patch-Clamp Techniques; Peptide Fragments - pharmacology; Protein Isoforms - genetics; Protein Isoforms - physiology; Scorpion Venoms - pharmacology; Scorpions; Sodium Channels - genetics; Sodium Channels - physiology; Xenopus laevis
• ISSN: 0026-895X; 1521-0111
• DOI: 10.1124/mol.106.022970

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 β 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 EC 50 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 μM, 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 EC 50 value of 1127 nM. Finally, the effects of OD1 were compared with a classic α-toxin, AahII from Androctonus australis Hector and a classic α-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.