Geraniol blocks calcium and potassium channels in the mammalian myocardium: useful effects to treat arrhythmias.

Abstract

Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca(2+) current, K(+) currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC=1,510±160μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the IC a,L was reduced by 50.7% (n=5) after perfusion with 300μM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n=5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K(+) current (Ito ) (59.7%, n=4), the non-inactivation K(+) current (Iss ) (39.2%, n=4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n=4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n=6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n=6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain-induced arrhythmias.