LAUSR

Abstract (‐)‐Terpinen‐4‐ol is a naturally occurring plant monoterpene and has been shown to have a plethora of biological activities. The objective of this study was to investigate the effects of (‐)‐terpinen‐4‐ol on the rat heart, a key player in the control and maintenance of arterial blood pressure. The effects of (‐)‐terpinen‐4‐ol on the rat heart were investigated using isolated left atrium isometric force measurements, in vivo electrocardiogram (ECG) recordings, patch clamp technique, and confocal microscopy. It was observed that (‐)‐terpinen‐4‐ol reduced contraction force in an isolated left atrium at millimolar concentrations. Conversely, it induced a positive inotropic effect and extrasystoles at micromolar concentrations, suggesting that (‐)‐terpinen‐4‐ol may have arrhythmogenic activity on cardiac tissue. In anaesthetized animals, (‐)‐terpinen‐4‐ol also elicited rhythm disturbance, such as supraventricular tachycardia and atrioventricular block. To investigate the cellular mechanism underlying the dual effect of (‐)‐terpinen‐4‐ol on heart muscle, experiments were performed on isolated ventricular cardiomyocytes to determine the effect of (‐)‐terpinen‐4‐ol on L‐type Ca2+ currents, Ca2+ sparks, and Ca2+ transients. The arrhythmogenic activity of (‐)‐terpinen‐4‐ol in vitro and in vivo may be explained by its effect on intracellular Ca2+ handling. Taken together, our data suggest that (‐)‐terpinen‐4‐ol has cardiac arrhythmogenic activity. Graphical abstract Figure. No Caption available.