Comparative analysis of electrophysiological characteristics
and excitation conduction in ventricular cardiomyocytes obtained from a healthy individual and a patient with the syndrome
of long QT interval
Abstract
Currently, it is known that most cardiac tachyarrhythmias are caused by the circulating excitation waves – reentry. The tissue-engineering models of cardiac tissue developed recently and employing optical mapping allow interactively observe the excitation propagation, record the formation of the reentry as a result of the interaction of excitation waves with various anatomical obstacles and see the direct response of propagating waves and the reentry to pharmaceuticals. The discovery of induced pluripotent stem cells and cellular reprogramming made by S. Yamanaka in 2006 opens up new possibilities for the production of human cardiomyocytes and makes tissue engineering models potentially promising. Moreover, for a number of cardiac diseases such as drug-induced long QT syndrome (aLQTS) there is no adequate animal model, so the use of human tissues becomes indispensable.
A detailed knowledge of the mechanisms of reentry formation can significantly increase the effectiveness of screening for potential antiarrhythmic drugs, and also develop treatment protocols to avoid serious side effect such as aLQTS and early afterdepolarizations (EADs).
In this paper we present results of the characterization of the generation and propagation of the excitation in human cardiac cells obtained by reprogramming from patients with congenital Long QT syndrome, type 2 (LQT2), caused by p.T613M mutation in the KCNH2 gene. The main characteristics of the “healthy”-derived and LQT2-derived cells layers were studied. The ion currents measured by the patch-clamp method on individual cells and the characteristics of the excitation wave in the cell layers carrying the mutation were compared with those measured in cultured cardiomyocytes obtained from the healthy individuals.
It was found that layers of the mutant cells characterized by decreased frequency of spontaneous activity, and increased probability of breaking of the unified rhythm determined by the pacemaker cells in addition to the lengthening the action potential.
Keywords:induced pluripotent cells, LQTS, KCNH2
Clin Experiment Surg. Petrovsky J. 2018; 6 (3): 6–15.
doi: 10.24411/2308-1198-2018-13001. Received: 27.06.2018. Accepted: 10.08.2018.
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