Identification of Ion Currents Components Generating Field Potential Recorded in MEA From hiPSC-CM

Abstract

The proposed strategy offers a possible answer to a major question raised by the community of safety pharmacology. By allowing a more automated analysis of the signals, our approach could contribute to promote the technology based on MEA and hiPSC-CMs and, therefore, improve reliability and efficiency of drug screening.

Identifying drug response by combining measurements of the membrane potential, the cytosolic calcium concentration, and the extracellular potential in microphysiological systems

“…From the definitions (16)- (19), we observe that for θ = 0, R * j = R j (λ 0 ) andH j (λ 0 , 0) = 0, implying that the known solution λ = λ 0 minimize (16) for θ = 0. Furthermore, for θ = 1, R * j (1) = R * j defined by the data,H j (λ, 1) = H j (λ), andH(λ, 1) = H(λ).…”

“…As mentioned above, the bidoman model has been used by many authors (see e.g., [18,16,19,20,14]) to simulate the electrophysiology of collections of hiPSC-CMs. One problem pointed out by several authors is the lack of a repolarization wave in the simulated results although the repolarization wave is clearly present in measurements of the extracellular potential; see, e.g., Figure 3 and Figure 4 of [18].…”

“…[17]) for this purpose. The bidomain model has already been used for inversion of U data (but not V and Ca) by several authors; see [18,16,19,20,14]. However, it is demonstrated in [18] that the bidomain model does not provide an extracellular repolarization wave.…”

Human iPSC-Derived Cardiomyocyte Networks on Multiwell Micro-electrode Arrays for Recurrent Action Potential Recordings

“…Beating embryoid bodies 11,12,13 and monolayer 3,7,10,11,12,13,14,15,16,17 differentiation are the preferred methods for cardiomyocyte production and the multielectrode array (MEA) has become a common modality for monitoring the electrodynamics of these networks 18,19,20 . While parameters that can be extracted from field potentials (FPs) such as beating rate, amplitude, duration and RR intervals are baseline electrophysiological responses of spontaneously beating monolayers 18,21,22,23 , the action potential (AP) components underlying these extracellular FP signals are difficult to extrapolate 24 . Our recent publication on the discovery of an application of MEAs for direct recurrent AP measurements provides proof of methodology for exemplary intracellular AP readouts with an extensive waveform analysis at various repolarization phases across multiple batches of hiPSC-derived cardiomyocyte networks 3 .…”

“…Additionally, this technology permits simultaneous FP/AP measurement generating electro-biome libraries in a short period of time. Given the growing emphasis on arrhythmia prediction and drug associated cardiotoxicity 24,32,33,34,35 , integration of AP measurement approaches will enhance drug safety and efficacy assessments.…”