• FLEXcyte 96

    Cardiomyocytes cultivated on a flexible membrane
  • FLEXcyte 96

    Measure true cardiac contractility
  • FLEXcyte 96

    The complete setup fits on a lab benchtop
  • FLEXcyte 96

    Judge compound responses at a glance

27.01.2021 | Webinar: Thinking outside the cardiac box

icon pl  Patchliner and Icon FLEX FLEXcyte 96 Webinar

Date: January 27. 2021

210127 webinar cardiac box

Speakers: 

Dr. Elena Dragicevic (Senior Sales and Alliance Manager; Nanion Technologies)

 

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 Cardiomyocytes2 in 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.


Back to Overview

FLEXcyte 96 Brochure

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.