Nonlinear Changes of Transmembrane Potential During Electrical Shocks

Abstract

Defibrillation shocks induce nonlinear changes of transmembrane potential (ΔV m ) that determine the outcome of defibrillation. As shown earlier, strong shocks applied during action potential plateau cause nonmonotonic negative ΔV m , where an initial hyperpolarization is followed by V m shift to a more positive level. The biphasic negative ΔV 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 ΔV 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 ΔV m was measured by optical mapping. Shock-induced negative ΔV m exhibited a biphasic shape starting at a shock strength of ≈15 V/cm when estimated peak ΔV − m was ≈−180 mV; positive ΔV 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 ΔV m , indicating the occurrence of membrane electroporation at these locations. The occurrence of biphasic negative ΔV 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 BaCl 2 , respectively, did not affect ΔV m , indicating that these currents were not responsible for biphasic ΔV m . These results provide evidence that the biphasic shape of ΔV m at sites of shock-induced hyperpolarization is caused by membrane electroporation.