Virtual Sources and Sinks During Extracellular Field Shocks in Cardiac Cell Cultures

Abstract

Background-One mechanism by which extracellular field shocks (ECFSs) defibrillate the heart is by producing changes in membrane potential (V m ) at tissue discontinuities. Such virtual electrodes may produce new excitation waves or affect locally propagating action potentials. The rise time of V m determines the required duration of a single defibrillation pulse to reach a critical threshold for activation or for the modification of ion channel function, and depends on the electric and microstructural characteristics of the tissue. Methods and Results-We used optical mapping of V m in patterned cultures of neonatal rat ventricular myocytes to assess the relationship between cardiac structure and the early time course of V m during ECFSs. At monolayer boundaries, the time course of V m showed a close fit to the theoretical change predicted by theory, with a membrane time constant of 2.65Ϯ0.19 ms (nϭ13) and a length constant of 159Ϯ6 m (nϭ10). Experiments in patterned strands, mimicking the resistive boundaries that occur naturally in the heart, explained the observation that the rate of rise and the maximal amplitudes of the V m changes are inversely related because of electrotonic interactions between structural boundaries. Interrupting ECFSs by very short intervals diminished V m , but did not cause major changes in its overall time course. Conclusions-Interaction between virtual sinks and sources decreases the magnitude of the changes in V m but accelerates its time course. For efficient defibrillation, short ECFSs are needed, with an amplitude adapted to match the boundary interaction. (Circ Arrhythm Electrophysiol. 2012;5:391-399.)

Complex Structure and Dynamics of the Heart

“…Further cell culture studies with carefully-prepared artificial boundaries of known curvature could take this verification to a quantitative level or indicate directions of improvement. Secondly, the reduced time scale for depolarization next to high-curvature circular boundaries found in section 3.2.13 is consistent with a recent study by A. Kondratyev et al, who found a considerably shorter time scale for the rise of the membrane potential in cell cultures of neonatal rat myocytes, if depolarized and hyperpolarized straight boundaries are in close proximity [221]. Thus, a qualitatively similar mechanism seems to be in effect for curved boundaries.…”