title: Nonlinear changes of transmembrane potential during electrical shocks: role of membrane electroporation.
abstract: Defibrillation shocks induce nonlinear changes of transmembrane potential (DeltaVm) that determine the outcome of defibrillation. As shown earlier, strong shocks applied during action potential plateau cause nonmonotonic negative DeltaVm, where an initial hyperpolarization is followed by Vm shift to a more positive level. The biphasic negative DeltaVm 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 DeltaVm and measuring uptake of membrane-impermeable dye. Experiments were performed in cell strands (width approximately 0.8 mm) produced using a technique of patterned cell growth. Uniform-field shocks were applied during the action potential plateau, and DeltaVm was measured by optical mapping. Shock-induced negative DeltaVm exhibited a biphasic shape starting at a shock strength of approximately 15 V/cm when estimated peak DeltaV-m was approximately -180 mV; positive DeltaVm 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 DeltaVm, indicating the occurrence of membrane electroporation at these locations. The occurrence of biphasic negative DeltaVm was also paralleled with after-shock elevation of diastolic Vm. Inhibition of I(f) and I(K1) currents that are active at large negative potentials by CsCl and BaCl2, respectively, did not affect DeltaVm, indicating that these currents were not responsible for biphasic DeltaVm. These results provide evidence that the biphasic shape of DeltaVm at sites of shock-induced hyperpolarization is caused by membrane electroporation.
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Ala 35294, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Cheek
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Fast
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004554:Electric Countershock; D018274:Electroporation; D005456:Fluorescent Dyes / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D005456:Fluorescent Dyes; D007473:Ion Channels; C024986:barium chloride; D002586:Cesium; D011419:Propidium; C028019:cesium chloride