Single Cell Experiments

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, 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 (I_to). When I_to is blocked with 4-aminopyridine (4-AP), 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. Action-potential clamp experiments, using Wenckebach rhythms previously recorded in the same cell as the imposed waveform, reveal a beat-to-beat decrease in I_to, paralleling the beat-to-beat changes in the slope of phase 1 and in APD. Simulations using an ionic model of I_to show cyclical changes in I_to consistent with the experimental data. These results demonstrate a key role for I_to in the generation of maintained periodic Wenckebach rhythms in isolated rabbit ventricular cells.