hiPSC-CM - "Conduction velocity with the 2-electrode layout of the CardioExcyte 96"
Cardiac conduction is the process by which electrical excitation spreads through the heart, triggering individual myocytes to contract synchronously. Slowed cardiac conduction velocity (CV) is associated with an increased risk of re-entrant excitation, leading to a pre-disposition to life-threatening arrhythmias1.
CV is determined by the ion channel properties of cardiac myocytes and by their interconnections. It is strictly dependent on the maximum upstroke velocity of an action potential, which is determined by the sodium current2. In addition, gap junctions play a key role because they ultimately determine how much depolarizing sodium current passes from excited to non-excited regions of the network. Uncoupling of gap junctions causes discontinuities leading to slower CV. Defective intercellular coupling between the cardiomyocytes results in increased subthreshold depolarization, which slowly inactivates the voltage-gated sodium channels, further reducing the sodium current and excitability3.
In the case of collagenous scar tissue the uncoupling of myocyte–myocyte connections and subsequent coupling of myocytes with fibroblasts impairs the electrical conduction. In fact, collagen deposition results in electrically isolated fibers of viable myocardium, discontinuing the conduction path and globally reducing the action potential propagation velocity and consequently promoting the onset of re-entrant arrhythmias4. Since CV plays a pivotal role in cardiovascular diseases, it is essential to investigate the effect of a new compound on the cardiac CV.
In this study, we have investigated the effect of the sodium channel blocker lidocaine (30 and 100 μM) on CV in hiPSC-CMs (NEXEL Cardiosight®-S) using the CardioExcyte 96.