Cardiac safety screens: molecular, cellular, and optical advancements

摘要

Identifying cardiac safety is becoming increasingly important for new drugs under development, since it is compulsory for the approval of almost all pharmaceutical drugs. In contrast to conventional electrophysiological in vitro assays that are based on a single entity, the hERG channel, primary cardiomyocytes based readouts seem to be more comprehensive. Such an action potential readout for those cells can be performed with contact-free optical methods. Here we reveal the details of both, the optical arrangement and the procedure to screen cardiac myocytes based on nave action potentials. Furthermore we evaluate the differences between neonatal and adult cardiac myocytes from rats based on a selection of test substances (quinidine, 4-aminopyridine and E-4031) and relate it to the human situation. Finally the results are discussed in the context of emerging genetically encoded potential sensors and latest development in optical detection technologies