Investigation of sodium channel Nav1.8 knock-out by CRISPR-Cas9 technology in human induced pluripotent stem cell cardiomyocytes

Project start
Institution: Department of Cardiology and Pneumology, Georg August University Göttingen
Applicant: Dr. Nico Hartmann
EKFS funding line: First and Second Applications
Image: Patch-Clamp-Setup

Heart failure is associated with arrhythmias and sudden cardiac death. Current data indicate that noncardiac sodium channel isoforms such as Nav1.8 lead to disruptions in cardiac electrophysiology. In order to investigate the importance of Nav1.8 and to show a link between Nav1.8-induced arrhythmia development, Nav1.8 knock-outs are generated in human, induced pluripotent stem cells using CRISPR-Cas9 technology and differentiated into cardiomyocytes. The electrophysiological mechanisms will be investigate through action potential and ion current measurements as well as through studies of cellular ion homeostasis. Using gene expression profiles and protein biochemistry, the underlying targets should be identified. By identifying the Nav1.8-mediated mechanisms, new translational antiarrhythmic therapeutic approaches can be generated.