Studying the associated electrical, structural and molecular mechanisms driving to aberrant repolarization heterogeneity in human heart – Rokhaya Faye

Cardiac excitability is controlled by a combination of depolarizing and repolarizing currents, whose dysregulation during heart failure (HF) or myocardial infarction (MI) play a significant role in relevant life-threatening cardiac arrhythmias. In addition, several studies have also shown that specific gene mutations which encode for cardiac potassium channel subunits are the principal cause of certain arrhythmias that result from abnormal repolarization phenotypes such as in the case of Long QT Syndrome 1 and 2 (LQTS1, LQTS2). However, the precise relationship between the expression and regulation of these potassium channels and arrhythmias is still not clear. In addition, many of these studies are conducted in animal models or cell lines.  To overcome this gap, I undertook of investigating the potential regulatory and/or modulatory role of key potassium channels: Iks and Ikr and Ito during abnormal repolarization. The experimental strategy here is to apply gene silencing approach by using short interfering RNA (siRNA) technique to mimic LQT disorder genotypes in organotypic ventricular slices from human donor hearts.