Key result
Evaluating drugs in isolated native cardiac myocytes yielded a dofetilide pIC50 of 7.3 and detected early afterdepolarizations, proving superior to cloned hERG channels for predicting TdP.
Isolated native cardiac myocytes are a better predictor of drug-induced QT prolongation and torsades de pointes than heterologously expressed hERG channels in early drug discovery.
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May improve early TdP prediction in drug screening; leaves open clinical translation from animal models.
Davie et al. (2004) studied QT interval prolongation and torsades de pointes. QT-prolonging drugs (e.g., dofetilide, E-4031, cisapride) vs. Cloned hERG channels in HEK293 cells was evaluated on Action potential duration, early afterdepolarizations, and I(Kr) inhibition. Evaluating drugs in isolated native cardiac myocytes yielded a dofetilide pIC50 of 7.3 and detected early afterdepolarizations, proving superior to cloned hERG channels for predicting TdP.
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