Evaluation of Phα1β Interaction on the Kv11.1 Potassium Channel in HEK293 Cells Trans-fected with the Human ERG Channel

• DOI: 10.20944/preprints202311.1407.v1
• Publication Date: 2023-11-23T06:05:40Z
• Authors: Joao Batista Calixto; Adara Aurea Santos; Juliano Ferreira; Alessandra Hubner...; Célio José Castro...; Marcus Vinicius G...

Phα1β a spider peptide, purified from the venom of Phoneutria nigriventer inhibits high voltage calcium channels and is antagonist of TRPA1 receptor two important pain transduction path-ways. In the last 15 years, we have showed, in preclinical tests with Phα1β native and recombi-nant in rodent models of pain the potential of Phα1β to become a new analgesic drug. Evaluation of new drug on human ERG channel is requirement of the regulatory agencies. For the hERG channel inhibition assay it was used the commercial kit FLIPR® Potassium Assay. It was tested the effect of Phα1β and as positive control dofetilide, a well characterized hERG block-er. Phα1β 56, 225, 450 and 900 pMol caused at a higher concentration a very weak inhibition of the hERG channel activity of about 13.47 % with channel inhibition at 50%, IC50 > 900 pMol. Dofetilide (0.0001 - 10 µM), a known hERG inhibitor, caused a well-known, concentra-tion-dependent inhibition of the hERG channel with a mean IC50 of 0.1642 µM (0.1189 – 0.2282 µM. For the cytotoxicity assay, Phα1β concentrations of 56, 225, 450 and 900 pMol incubated for 24 h with HEK293-hERG cells did not alter the viability of the HEK293-hERG cells. It is con-cluded that Phα1β even at high concentrations does not interfere with hERG channels.