Antiarrhythmic properties of Botulinum toxin A: in vitro studies on human and rat cardiomyocytes

Abstract Botulinum toxin A is a well-known neurotransmitter inhibitor with a wide range of applications in modern medicine. In recent years, botulinum toxin preparations have begun to be used in clinical trials to suppress cardiac arrhythmias, especially in the postoperative period. Its antiarrhythmic action is associated with inhibition of the nervous system of the heart, but the question of a direct effect on heart tissue remains unclear. In our work, we investigate the effect of botulinum toxin on isolated cardiac cells and on layers of cardiac cells capable of conducting excitation. As an object of research, cardiomyocytes of neonatal rat pups and human cardiomyocytes obtained through cell reprogramming were used. A patch-clamp study showed that the botulinum toxin inhibited fast sodium currents and L-type calcium currents in a dose-dependent manner, with no apparent effect on potassium currents. It was shown by optical mapping that in the presence of the botulinum toxin, the propagation of the excitation wave in the layer of cardiac cells slows down sharply, conduction at high concentrations becomes chaotic, but reentry waves do not form. It was found that the combination of the botulinum toxin with a preparation of chitosan has a stronger inhibitory effect by an order of magnitude. It was demonstrated that the inhibitory effect of the botulinum toxin is not permanent and disappears after 12 days of cell culture in a botulinum toxin-free medium.