Calcium overload-induced arrhythmia is suppressed by farnesol in rat heart

Abstract

Cardiac arrhythmias are among the most important pathologies that lead to sudden death. The discovery of new therapeutic options against arrhythmias with low adverse effects is of paramount importance. Farnesol is found in essential oils with antioxidant, anti-inflammatory and cardioprotective properties. The aim of this work was to investigate the effects of farnesol on the contractile and electrophysiological properties in rat heart and evaluate its antiarrhythmic action. It was evaluated farnesol effects on the left ventricular developed pressure, ECG, potassium (I_k) and L-type Ca²⁺ currents (I_Ca,L), action potential, intracellular Ca²⁺ transient, Ca²⁺ sparks and waves and reactive oxygen species production. Antiarrhythmic activity of farnesol was determined in vivo and ex vivo. The results showed that 50 μM farnesol did not alter left ventricular developed pressure, heart rate, ECG parameters and intracellular Ca²⁺ transient but reduced I_Ca,L. Farnesol reduced action potential duration at 90% repolarization. Notably, farnesol improved arrhythmia score and the incidence of the most severe arrhythmias. Farnesol attenuated the generation of reactive oxygen species, Ca²⁺ sparks and waves in isolated cardiomyocytes submitted to Ca²⁺ overload. In conclusion, farnesol has antiarrhythmic effect mediated by reducing of I_Ca,L and I_K along with a decrease of reactive oxygen species production and normalized Ca²⁺ sparks and waves.

Keywords: Arrhythmia; Ca(2+) sparks; Farnesol; K(+) currents; L-type Ca(2+) channels; Oxidative stress.