Blocking effects of acehytisine on pacemaker currents (I(f)) in sinoatrial node cells and human HCN4 channels expressed in Xenopus laevis oocytes.

The root of Aconitum coreanum (Levl.) Raipaics has been extensively used to treat various kinds of disorders including cardiovascular disease in China for a long time. According to recent studies, its antiarrhythmic actions are attributable to the active component, acehytisine. However, the underlying mechanism remains poorly understood. The effects of acehytisine on the spontaneous activity in sinoatrial nodes and the electropharmacological action of this drug on I(f) in pacemaker cells and hHCN4 channels in oocytes were to be investigated. Sinoatrial nodes were cut from rabbit heart, and transmembrane potentials were recorded by standard microelectrode technique. A whole-cell patch clamp technique was employed to record I(f) isolated enzymatically from rabbit sinoatrial node pacemaker cells. Human HCN4 channels were heterologously expressed in Xenopus oocytes and studied using the two-electrode voltage clamp technique. Acehytisine decreased the pacemaker rate of firing and slope of diastolic depolarization, modified the action potential configurations and blocked I(f) in rabbit sinoatrial node cells and hHCN4 channels expressed in Xenopus oocytes in a concentration-dependent, voltage-independent and non-use-dependent manner. Its electropharmacological properties were consistent with those of a close-state blocker. Our findings are likely to shed light on the clinical application of acehytisine in the treatment of cardiovascular disorders.