Nonlinear Changes of Transmembrane Potential, during Electrical Shocks: Role of Membrane Electroporation

Academic Article

Abstract

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

    Author List

  • Cheek ER; Fast VG
  • Start Page

  • 208
  • End Page

  • 214
  • Volume

  • 94
  • Issue

  • 2