Electrochemical strategy to scout 1,4-naphthoquinones effect on voltage gated potassium channels

• Published in: Bioelectrochemistry (Amsterdam, Netherlands) Netherlands), 2012-08, Vol.86, p.1-8
• Main Authors: Rodríguez-Fernández, T., Ugalde-Saldívar, V.M., González, I., Escobar, L.I., García-Valdés, J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cyclic voltammetry; Dimethyl Sulfoxide; Electrochemistry - methods; Electrophysiological Phenomena; Female; Hydrogen Bonding; Ion channel; Kv1.3 Potassium Channel - antagonists & inhibitors; Kv1.3 Potassium Channel - chemistry; Kv1.3 Potassium Channel - metabolism; Molecular Sequence Data; Naphthoquinones; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Oocytes - drug effects; Potassium Channel Blockers - pharmacology; Potassium Channels, Voltage-Gated - antagonists & inhibitors; Potassium Channels, Voltage-Gated - chemistry; Potassium Channels, Voltage-Gated - metabolism; Protein Structure, Tertiary; Redox potential; Shaker Superfamily of Potassium Channels - antagonists & inhibitors; Shaker Superfamily of Potassium Channels - chemistry; Shaker Superfamily of Potassium Channels - metabolism; Voltage-gated potassium channel; Xenopus laevis
• ISSN: 1567-5394; 1878-562X
• DOI: 10.1016/j.bioelechem.2011.12.010

Naphthoquinone (NQ) was tested on voltage-gated ion channels expressed in Xenopus laevis oocytes. The activity of potassium Shaker channel with Inactivation domain Removed (ShIR) was not affected; in contrast, NQ diminished Kv1.3 currents. A current decrease was barely observed with the oxidant H2O2. These findings suggested that redox properties were involved in the naphthoquinone–Kv1.3 channel interaction. NQ and some derivatives (NQs) were characterized in DMSO and physiological (ND-96) media by cyclic voltammetry. A typical two-stage mono-electronic reduction mechanism was observed in DMSO, while a one-stage bi-electronic reduction process was found in ND-96 medium. NQs with the lowest and the highest redox potential values were tested on both channels. Voltage-clamp recordings showed that inhibition of Kv1.3 was dependent on NQs redox potential. Results demonstrated that structural features (aromaticity and substituents prone to hydrogen bonds formation) of NQs were also important. This effect could be explained by interactions of some channel residues with NQs that contribute to favor their reduction process in the protein surroundings. The electrochemical strategy presented to simulate the cellular environments (aqueous and non-aqueous) that NQs may face, is an important contribution to pre-select (in a fine and simple way) the best redox compounds for electrophysiological testing. ►In water, naphthoquinone derivatives (NQs) reduce at different redox potential. ►NQs inhibit Kv1.3 ion channel and have no effect on Shaker ion channel. ►Kv1.3 modulation depends on NQs redox potential and structural features. ►Electrochemistry helps to select redox compounds to be tested on ion channels.