Figure 3. hCMC for real-time detection of API adverse effects.

(A) The recorded field potential of one hCMC at the beginning (control) and after application of 100 µM noradrenaline. The comparison of the concentration response curve for the accumulative (n  = 6 hCMC) and discrete application (n  = 3 hCMC) of noradrenaline reveals considerably different EC₅₀ values. (B) Analysis of adverse side effects like QT interval relevant APD prolongation can be detected and quantified. While E4031 has an influence on contraction rate at higher concentrations, the application of 1 nM results in a prolonged fAPD after 15 minutes. The analysis of the frequency-corrected fAPD (fAPD_c) revealed an EC₅₀ of 7.2 nM (n  = 13 hCMC), (blue bar – published EC₅₀ range obtained from hERG-channel assay, green bar – published EC₁₀ range of in vivo studies in dogs, monkeys and humans).