Ion channel basis for alternans and memory in cardiac myocytes

Beat-to-beat alternation in action potential morphology (alternans) in individual cardiac cells may be important in the development of ventricular tachycardia and fibrillation. So far, it has been difficult to identify the cause for alternans at the ion channel level because computer models and experiments that display alternans also simultaneously exhibit other confounding rhythm patterns, including those attributable to short timescale memory effects. To address this difficulty, we have developed an eigenmode method to study the dynamics of detailed cardiac cell models under constant pacing. The method completely separates these effects from one another in the linear regime, allowing each to be studied individually. For the Beeler-Reuter ion channel model, the fundamental difference between the alternans and memory modes was found to be rooted in the difference in the relative phasings of the x1 and f gate perturbations associated with the slow outward and slow inward currents, respectively. The importance of this relative phasing was analyzed with the help of two new analytical methods. For the alternans case, the relative phasing produced constructive interference between the two currents large enough to reverse the perturbation in membrane potential from beat to beat. The opposite was true of the memory mode.