Theoretical and experimental study of sawtooth effect in isolated cardiac cell-pairs

Introduction: The question of how a defibrillation shock affects the myocardium far (> ∼1 mm; the space constant of continuum tissue models) from the electrode is not fully understood. According to a long-standing, yet to be verified, hypothesis, the relatively high-resistance intercellular gap junctions may help in coupling the shock effect to the distant myocardium by redistributing the defibrillation current and creating a sawtooth pattern of polarization in which every cell undergoes hyperpolarization and depolarization. The goal of this study was to conduct an in-depth theoretical and experimental investigation of the sawtooth effect in the simplest coupled system, that of an isolated cell-pair. Methods and Results: Theoretically, we present a relationship between sawtooth amplitude (STA) and junctional resistance (R_j), and show that, in a cell-pair with two cells of different lengths, the sawtooth effect may not necessarily appear as a reversal in polarization across the junction when R_j is below a critical value. Experimentally, we optically mapped transmembrane potential responses along the lengths of enzymatically isolated guinea pig cell-pairs at 10- or 17-μm resolution, and estimated STA as the magnitude of discontinuity in responses at the intercellular junction. From 14 cell-pairs, STA was estimated to be ∼11 mV for a nominal 10 V/cm field. Based on our theoretical results, this value corresponds to an R_j of ∼18 MΩ. Conclusion: The intercellular junction induces a measurable sawtooth effect in the simplest system of an isolated cell-pair. An accounting for the sawtooth effect might be essential for understanding field-tissue interaction far from the electrode and to accurately predict tissue response during field stimulation.