Published online before print December 11, 2003, doi: 10.1161/01.RES.0000111526.69133.DE
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Submitted on July 18, 2003
Revised on November 24, 2003
Accepted on November 25, 2003
Nonlinear Changes of Transmembrane Potential During Electrical Shocks. Role of Membrane Electroporation
Eric R. Cheek and Vladimir G. Fast *
From the Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Ala.
* To whom correspondence should be addressed. E-mail: fast{at}crml.uab.edu.
Defibrillation shocks induce nonlinear changes of transmembrane potential (
Vm) that determine the outcome of defibrillation. As shown earlier, strong shocks applied during action potential plateau cause nonmonotonic negative Vm, where an initial hyperpolarization is followed by Vm shift to a more positive level. The biphasic negative Vm 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 Vm 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 Vm was measured by optical mapping. Shock-induced negative Vm exhibited a biphasic shape starting at a shock strength of 15 V/cm when estimated peak V-m was -180 mV; positive Vm 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 Vm, indicating the occurrence of membrane electroporation at these locations. The occurrence of biphasic negative Vm was also paralleled with after-shock elevation of diastolic Vm. Inhibition of If and IK1 currents that are active at large negative potentials by CsCl and BaCl2, respectively, did not affect Vm, indicating that these currents were not responsible for biphasic Vm. These results provide evidence that the biphasic shape of Vm 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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