“Electrophysiology of long-term culture of adult human myocardium”

Genetic manipulation and regulation of ion channel expression has been studied thoroughly in a large variety of animal models and in cell culture. However, the clinical translation of the results of these studies has been hampered by significant differences in genetics, cell and tissue physiology between various animal models, on the one hand, and human patients, on the other hand. Recent advent of iPS cell technology presented exciting opportunities to study cardiac physiology in human cell lines, including patient-specific iPS cell derived myocytes. However, it remains impossible to manipulate gene and protein expression in adult human myocardium. The goal of this project is to produce such a versatile open source platform by using adult human ventricular slices that can be cultured for at least 1-4 weeks allowing application of viral vector and RNAi methods to regulate protein expression related to electrical activity in the human myocardium. We aim to develop and validate this platform, focusing on ion channels, connexins, and calcium handling proteins as they remodel during heart failure.