The all-or-none repolarization in cardiac ventricular myocytes: an in silico characterization of a relevant biomarker of ventricular action potential

All-or-none repolarization (AONR) consists in the fact that brief hyperpolarizing current injections delivered during the early phase of the cardiac action potential (AP) can reach membrane potential values where small changes in the current can either lead the post-injection membrane potential to recover the previous AP waveform or suddenly repolarize to the resting state. The phenomenon, long known from the early studies on squid axon and Purkinje fibers, has been studied over the years. Here, by means of an updated human ventricular AP model, the form of AONR is described in detail, showing how it is modified by the pacing rate and by the changes in the ion channels active during the early phase of AP. A novel representation of AONR is proposed that makes it easier to appreciate the features of this phenomenon and its relationship with the corresponding AP. It is shown, for example, how the threshold for AONR changes in different models of human ventricular AP. The phenomenon is revisited by which different propensity to generate AONR in endocardial and epicardial cells can lead to transmural repolarization gradients and arrhythmias. It is also shown that the form of AONR is mostly independent from the corresponding AP waveform, as two almost identical AP waveforms show completely different thresholds for AONR. The main message of this study is that the threshold for AONR is an easily accessible feature of the AP, rich in information concerning AP dynamics, which should be taken into consideration as a fundamental electrophysiological biomarker in the process of fine-tuning human ventricular AP models.