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16.02.2021: On-Demand Webinar Alert - Thinking Outside the Cardiac Box

Thinking Outside the Cardiac Box: Ion channel physiology in iPSC-CMs in a virtual or mechanically induced pro-maturation environment

Watch Dr. Elena Dragicevic present the following talk at iForum™ 2021 Virtual User Group Meeting:

 

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are attractive due to their unlimited availability and human origin, making them a promising tool for cardiac research and safety pharmacology. However, they can show an immature phenotype such as lower inward rectifier potassium current (IK1), atypical expression pattern of ion channels, divergent response to pharmacological agents and contractile behaviour compared to adult CMs. Thus, their detailed characterization and optimized recording environments are essential.

We aimed to characterize and modulate electrophysiological and contractile properties of hiPSC-CMs using automated dynamic clamp and contraction measurements on flexible substrate.  

Here, we recorded iCell Cardiomyocytesin voltage and current clamp using a combined automated patch clamp (APC) and dynamic clamp device (Patchliner Dynamite8), and contractility recordings were made using the FLEXcyte 96. During the APC recordings simulated IK1 and seal compensation were applied to up to 8 hiPSC-CMs simultaneously, while the contractility recordings were conducted in 96-well plates. We have tested various compounds targeting cardiac ion channels and recorded their effects on action potential duration (APD), sodium, calcium and potassium currents, as well as their effect on the contraction capabilities of these cells. Additionally, different levels of static and cyclic pressure were applied to the cell monolayers with the aim to induce membrane deflection for reproducibility test of Frank-Starling mechanism and to imitate the physiological stretching experienced by CMs in the beating human heart during systolic and diastolic phases, respectively.

Seal compensation and virtual IK1 in hiPSC-CMs resulted in more stable and longer APs with low APD variability. Consequently, the dynamic clamp approach enabled reliable calcium, sodium and potassium channel pharmacology on action potentials of these cells. Culturing conditions that support contractility, i.e. flexible membrane substrates, demonstrate Ca2+ channel pharmacology equivalent to that expected from adult CMs while applied mechanical stimulation resulted in functional changes of hiPSC-CMs physiology.


Learn more about hiPSC-CMS

Application Note: Chronic cardiotoxic effects of tyrosine kinase inhibitors and anthracyclines analyzed with the FLEXcyte 96 on human iPSC-derived cardiomyocytes

Publication: Automated Dynamic Clamp for Simulation of IK1 in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes in Real Time Using Patchliner Dynamite8


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