Sulfur dioxide derivative prevents the prolongation of action potential during the isoproterenol-induced hypertrophy of rat cardiomyocytes

Exogenous SO2 is toxic especially to the pulmonary and cardiovascular system, similar to nitric-oxide, carbon-monoxide, and hydrogen-sulfide. Endogenous SO2 is produced in many cell types. The SO2 content of the rat heart has been observed to substantially decrease during isoproterenol-induced hypertrophy. This study sought to determine whether an SO2 derivative could inhibit the prolongation of action potentials during the isoproterenol-induced hypertrophy of rat cardiomyocytes and explore the ionic currents. Alongside electrocardiogram recordings, the voltage and current- clamped measurements were conducted in the enzymatically isolated left ventricular cardiomyocytes of Wistar rats. The consistency of the results was evaluated by the novel mathematical electrophysiology model. Our results show that SO2 significantly blocked the prolongation of QT-interval and action potential duration. Furthermore, SO2 did not substantially affect the Na+ currents and did not improve the decreased steady- state and transient outward K+ currents, but it reverted the reduced L-type Ca2+ currents (ICaL) to the physiological levels. Altered inactivation of ICaL was remarkably recovered by SO2. Interestingly, SO2 significantly increased the Ca2+ transients in hypertrophic rat hearts. Our mathematical model also confirmed the mechanism of the SO2 effect. Our findings suggest that the shortening mechanism of SO2 is related to the Ca2+ dependent inactivation kinetics of the Ca2+ current.This study was supported in part by Akdeniz University Scientific Research Coordination Unit (Project No: 2012.02.0122.009) and The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 117F020). These funding sources had no involvement in study design, writing of the report, decision to publish, or the collection, analysis, and interpretation of data

Classification of diabetic cardiomyopathy-related cells using machine learning

The patch-clamp technique is a significant tool in current electrophysiology research, especially in cardiovascular diseases, because it can capture electrical activity of the heart from cardiomyocytes. It is challenging to classify action potential waveforms in cardiological data from these recordings because it relies largely on professional assistance. We discovered that supervised classification may be used to predict the impact of electrophysiological perturbations on cardiomyopathic action potential groups in rat ventricular cells. At the cellular level, action potential classifications are utilized to discern between pathological and control waveforms in recorded cardiac action potentials. The four groups are as follows: (1) control, (2) diabetes, (3) diabetes with angiotensin, and (4) angiotensin. The signal’s biologically relevant features for the treatment of cardiomyopathy have been discovered. After they have been trained with different sets of features, the results of the seven machine learning models are compared. The knearest neighbor approach, along with the decision tree and random forest algorithms, is the best classifier for diagnosing aberrant action potential waveforms, with an accuracy of above 99% when compared to other models. The high classification accuracy demonstrates that the gathered individual cardiac AP features provide useful information regarding the pathological status of cardiomyocytes.No sponso

Mathematical model of the ventricular action potential and effects of isoproterenol-induced cardiac hypertrophy in rats

Mathematical action potential (AP) modeling is a well-established but still-developing area of research to better understand physiological and pathological processes. In particular, changes in AP mechanisms in the isoproterenol (ISO) -induced hypertrophic heart model are incompletely understood. Here we present a mathematical model of the rat AP based on recordings from rat ventricular myocytes. In our model, for the first time, all channel kinetics are defined with a single type of function that is simple and easy to apply. The model AP and channels dynamics are consistent with the APs recorded from rats for both Control (absence of ISO) and ISO-treated cases. Our mathematical model helps us to understand the reason for the prolongation in AP duration after ISO application while ISO treatment helps us to validate our mathematical model. We reveal that the smaller density and the slower gating kinetics of the transient K+ current help explain the prolonged AP duration after ISO treatment and the increasing amplitude of the rapid and the slow inward rectifier currents also contribute to this prolongation alongside the flux in Ca2+ currents. ISO induced an increase in the density of the Na+ current that can explain the faster upstroke. We believe that AP dynamics from rat ventricular myocytes can be reproduced very well with this mathematical model and that it provides a powerful tool for improved insights into the underlying dynamics of clinically important AP properties such as ISO application.This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 117F020). These funding sources had no involvement in study design, writing of the report, decision to publish, or the collection, analysis, and interpretation of data