Significance of stretch-activated ion channels for the electrophysiology of the ventricular myocardium

The present project aims to characterize the significance of stretch-activated ion currents for the electrophysiology of the ventricular myocardium. Ventricular arrhythmias occur more frequently in diseases associated with intracardiac pressure and volume overload. Stretch-activated channels (SACs) may mediate electrophysiological effects that lead to increased arrhythmia susceptibility. The recent availability of specific SAC blockers—particularly the tarantula peptide GSMTX-4—has made it possible to further define the role of stretch-activated ion currents in arrhythmia susceptibility. Initially, pressure and stretch stimuli of varying duration and intensity will be applied to the isolated heart, and the arrhythmogenic effect will be quantified using electrocardiography and action potential recording. Subsequent SAC blockade will demonstrate suppression of arrhythmia susceptibility and identify underlying mechanisms. If the hypothesis that stretch-activated channels have a decisive influence on the development of arrhythmias during ventricular stretch is confirmed, specific SAC blockade may offer a new treatment option.