Electrophysiological Properties of hiPSC CMs as Measured Using a 60-Electrode MEA Chamber
(A) Left, image of the 60-electrode MEA system, plated with monolayer of hiPSC CM. Superimposed on the image are the individual electrograms recorded at each electrode position. Center-left view is an example of methodology used to calculate the ARI. Green trace represents a single beat recorded at one lead of the MEA, showing depolarization and repolarization complexes, reminiscent of QRS and T waves. The ARI is calculated as time between the minimum first derivative of voltage (dV/dt) in the depolarization wave and the time of maximum dV/dt near the peak of the repolarization wave (bounded by the yellow lines). Blue trace represents dV/dt curve of the repolarization wave, used to determine maximum dV/dt. Center-right view shows example traces of consecutive spontaneous beats recorded at a single MEA site. ARIs for each lead were averaged to obtain a mean ARI value at each site for the duration of the recording. Right view is a representative electrogram recorded under control conditions and after perfusion with 10 and 100 nM dofetilide. Note the prolongation of the repolarization wave with increasing concentrations of dofetilide.
(B) Isochronal time maps from a typical MEA chamber demonstrating AT (Act) across the array, ARI (a surrogate for APD), and conduction velocity (CV). Act and ARI are reported in ms. CV is reported as cm/s.
(C) CMs differentiated from three different iPSC lines (C1, C6, and C7) exhibit similar electrophysiological properties. Box plots show mean (square), SEM (box), SD (error bars), and 95% confidence intervals (crosshatch). No significant differences were detected within cell lines with respect to the ARI, cycle length, and conduction velocity (n = 10–13 independent recordings).