Although impedance has been increasingly used to detect the proarrhythmic and contractile abnormalities in iPSC cardiomyocytes (CM), there are still ambiguities in interpreting impedance signals to explore the mechanisms of drug actions. In the present study, we have measured the impedance signals with xCELLigence CardioECR and sequential live imaging with CQ1 to examine the correlation of impedance with Ca2+ transients, action potentials, and muscle motion in the same preparation of iCell CM2. Beat duration of impedance signals showed the frequency dependent nature as with those of action potential, and had good correlation with Ca2+ signals in the change of signal duration induced by CiPA II non-core site compounds. Early afterdepolarization induced by cisapride could be identified more clearly in the Ca2+ or action potential signals than impedance ones. The peak amplitude was reduced by the calcium channel blockade in any of impedance, Ca2+ and motion signals, but the correlation among these signals was not likely to be clear compared with those of duration parameters. The combination of impedance signals and imaging data can be a strong tool to elucidate mechanisms of drug action on iPSC CM.

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