Abstract-The purpose of this study was to determine the spatial changes in the transmembrane potential caused by extracellular electric field stimulation. The transmembrane potential was recorded in 10 guinea pig papillary muscles in a tissue bath using a double-barrel microelectrode. After 20 S1 stimuli, a 10-ms square wave S2 shock field with a 30-ms S1-S2 coupling interval was given via patch shock electrodes 1 cm on either side of the tissue during the action potential plateau. Two shock strengths (2.1Ϯ0.2 and 6.5Ϯ0.6 V/cm) were tested with both shock polarities. In the macroscopic group, the portion of the tissue toward the anode was hyperpolarized, whereas the portion toward the cathode was depolarized, with 1 zero-potential crossing from hyperpolarization to depolarization present near the center of the tissue. In the microscopic group, only 1 zero-potential crossing was observed in the center region of the tissue, whereas, away from the center, only hyperpolarization was observed toward the anode and depolarization toward the cathode. Although these results are consistent with predictions from field stimulation of continuous representations of myocardial structure, ie, the bidomain and cable equation models, they are not consistent with the prediction of depolarization-hyperpolarization oscillation from representations based on cellular-level resistive discontinuities associated with gap junctions, ie, the sawtooth model. (Circ Res. 1998;83:1003-1014.)Key Words: hyperpolarization Ⅲ defibrillation Ⅲ simulation T o understand the mechanism of ventricular defibrillation, it is important to acquire knowledge of the transmembrane potential changes (⌬V m ) caused by the shock in addition to the action potential changes after the shock. This is because the cellular excitation and alteration in action potentials that occur after a defibrillation shock are thought to result from the changes in the transmembrane potential caused by the shock. 1,2 Several studies have been performed to obtain such information. Some studies used optical recording techniques to evaluate the ⌬V m caused by the shock field in either isolated myocytes 1,3-5 or perfused hearts. 2,6 -10 With a few exceptions, 1,3-5,11 the optical recording represents the weighted average of the ⌬V m changes in many cells. 2,7,9 Recordings of the transmembrane potential by a doublebarrel microelectrode can supply information about the ⌬V m caused by the shock from an individual cell within the myocardial syncytium. 12,13 A range of modeling studies completed over the past 15 years suggests that shock-induced ⌬V m can change markedly over the length of an individual cell.14 -17 These studies are based on the hypothesis that highly resistive gap junctions located at the cell ends create a sawtooth pattern of depolarization-hyperpolarization oscillation in the spatial distributions of V m . Experimentally, the sawtooth pattern has been observed during shocks applied to isolated myocytes, 1 with the cell end closest to the cathode depolarized and the end close...