Transient outward current contributes to Wenckebach-like rhythms in isolated rabbit ventricular cells

Wenckebach-like rhythms in isolated rabbit ventricular cells are characterized by beat-to-beat increments in action potential duration (APD) and latency, giving rise to a beat-to-beat decrease in the recovery interval and culminating in a skipped beat. These systematic APD changes are associated with a beat-to-beat decrease in the slope of the early repolarizing phase (phase 1) of the action potential, which is partially controlled by the transient outward potassium current (Ito). When Ito is blocked with 4-aminopyridine, periodic Wenckebach rhythms are replaced by aperiodic Wenckebach rhythms, in which the beat-to-beat changes in the slope of phase 1 and in APD disappear but the beat-to-beat increase in latency remains. A beat-to-beat decrease in Ito, paralleling the beat-to-beat changes in the slope of phase 1 and in APD, is seen in action-potential clamp experiments with Wenckebach rhythms previously recorded in the same cell. Simulations with an ionic model of Ito show cyclical changes in Ito consistent with the experimental data. These results demonstrate a key role for Ito in the generation of maintained periodic Wenckebach rhythms in isolated rabbit ventricular cells.