On the ionic mechanism of cyproheptadine-induced bradycardia in a rabbit sinoatrial node preparation

The effects of cyproheptadine (0.1-10 microM) on the membrane potentials and currents of rabbit sinoatrial node were examined with the double-microelectrode voltage clamp technique. Cyproheptadine reduced the heart rate, maximum rate of depolarization and action potential amplitude. It also decreased the slope of phase 4 depolarization. On the current systems, cyproheptadine decreased the slow inward current (Isi), the time-dependent potassium outward current (Ik) and the hyperpolarization-activated current (Ih). The reduction of Isi was the major effect. Furthermore, Isi was progressively decreased by repetitive membrane depolarization during administration of cyproheptadine, an effect suggestive of frequency-dependent block of Isi. These electrophysiological observations indicate that cyproheptadine has a calcium antagonistic property, and additionally, decreases Ik and Ih in rabbit sinoatrial node.