Brugada syndrome (BrS) is an inherited disease characterized by right precordial ST-segment elevation on electrocardiograms (ECGs), and a high risk of life-threatening ventricular arrhyth-mia and sudden cardiac death. In BrS patients, except for SCN5A, mutations in other responsible genes are poorly elucidated. We identified a new missense mutation, c.1189C>T (p.R397C), in the KCNH2 gene in asymptomatic male proband with diagnosed BrS. We performed patch-clamp analysis on I(Kr) reconstituted with this KCNH2 mutation in Chinese hamster ovary cells and compared the phenotype with the wild type. We found that the R397C mutation increased the I(Kr) density. In silico modeling demonstrated that this missense mutation potentially leads to the shortening of action potential in the heart.

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.