Theoretical and Experimental Study of Sawtooth Effect in Isolated Cardiac Cell‐Pairs

Sawtooth Effect in 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 M Ω. 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 fieldtissue interaction far from the electrode and to accurately predict tissue response during field stimulation.