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Nonlinear Changes of Transmembrane Potential During Electrical Shocks

Role of Membrane Electroporation

From the Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Ala.

Correspondence to Vladimir G. Fast, PhD, University of Alabama at Birmingham, 1670 University Blvd, VH B149, Birmingham, AL 35294. E-mail fast{at}crml.uab.edu

Defibrillation shocks induce nonlinear changes of transmembrane potential (V_m) that determine the outcome of defibrillation. As shown earlier, strong shocks applied during action potential plateau cause nonmonotonic negative V_m, where an initial hyperpolarization is followed by V_m shift to a more positive level. The biphasic negative V_m can be attributable to (1) an inward ionic current or (2) membrane electroporation. These hypotheses were tested in cell cultures by measuring the effects of ionic channel blockers on V_m and measuring uptake of membrane-impermeable dye. Experiments were performed in cell strands (width 0.8 mm) produced using a technique of patterned cell growth. Uniform-field shocks were applied during the action potential plateau, and V_m was measured by optical mapping. Shock-induced negative V_m exhibited a biphasic shape starting at a shock strength of 15 V/cm when estimated peak V^-_m was -180 mV; positive V_m remained monophasic. Application of a series of shocks with a strength of 23±1 V/cm resulted in uptake of membrane-impermeable dye propidium iodide. Dye uptake was restricted to the anodal side of strands with the largest negative V_m, indicating the occurrence of membrane electroporation at these locations. The occurrence of biphasic negative V_m was also paralleled with after-shock elevation of diastolic V_m. Inhibition of I_f and I_K1 currents that are active at large negative potentials by CsCl and BaCl₂, respectively, did not affect V_m, indicating that these currents were not responsible for biphasic V_m. These results provide evidence that the biphasic shape of V_m at sites of shock-induced hyperpolarization is caused by membrane electroporation.

Key Words: defibrillation • fluorescent imaging • membrane electroporation • virtual electrodes • secondary sources

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