Electroporation of Cardiac Cell Membranes with Monophasic or Biphasic Rectangular Pulses

Tovar, Oscar H.; Tung, Leslie

doi:10.1111/j.1540-8159.1991.tb02785.x

Cited by 93 publications

(45 citation statements)

References 5 publications

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“…This is significantly lower than the electroporation threshold of Ϸ300 mV reported from measurements of changes in membrane conductance in single frog myocytes in response to 5-ms-long voltage pulses. 25,26 The difference in thresholds between this and the present study could be attributable to differences in the pulse duration, different experimental conditions, as well as different cell species.…”

Section: Role Of Membrane Electroporation In Biphasic ⌬V Mcontrasting

confidence: 59%

Nonlinear Changes of Transmembrane Potential During Electrical Shocks

Cheek

Fast

2004

Circulation Research

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Abstract-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 Ϸ0.8 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 Ϸ15 V/cm when estimated peak ⌬V Ϫ m was ϷϪ180 mV; positive ⌬V m remained monophasic. Application of a series of shocks with a strength of 23Ϯ1 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 BaCl 2 , 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 Ⅲ fluorescent imaging Ⅲ membrane electroporation Ⅲ virtual electrodes Ⅲ secondary sources T he success or failure of defibrillation is determined by the magnitudes and the distribution patterns of shockinduced changes of transmembrane potential (⌬V m ), but the mechanisms governing the ⌬V m dynamics are not well understood. Experiments in cardiac tissue have shown that unlike in mathematical models, shocks produce strongly nonlinear V m responses. Shocks applied in the plateau phase of the action potential (AP) typically produce two basic types of nonlinear ⌬V m . The first type is characterized by a monotonic ⌬V m shape and an asymmetric distribution of ⌬V m magnitude, with the negative ⌬V m being much larger than positive ⌬V m . [1][2][3][4][5][6][7] Stronger shocks induce ⌬V m of the second type, which is characterized by a nonmonotonic behavior of negative ⌬V m when strong hyperpolarization is followed by a positive V m shift. 4,5 In addition, the amplitudes of both positive and negative ⌬V m do not increase proportionally with increasing shock strength but reach saturation levels and then decrease. 1,5 Several studies investigated cellular and ionic mechanisms of nonlinear ⌬V m . It was found that the asymmetry of V m response was reduced by the application of nifedipi...

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Section: Role Of Membrane Electroporation In Biphasic ⌬V Mcontrasting

confidence: 59%

Nonlinear Changes of Transmembrane Potential During Electrical Shocks

Cheek

Fast

2004

Circulation Research

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“…There is no detailed knowledge about these processes. Electroporation can be one of the outcomes and has been observed in experiments with single cells (15) and cardiac tissue preparations (17,33,48). Its presence in our experiments was indirectly supported by staining with propidium iodide (Fig.…”

Section: Discussionsupporting

confidence: 54%

Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage

Sambelashvili

Nikolski

Efimov

2004

American Journal of Physiology-Heart and Circulatory Physiology

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The virtual electrode polarization (VEP) effect is believed to play a key role in electrical stimulation of heart muscle. However, under certain conditions, including clinically, its existence and importance remain unknown. We investigated the influence of acute tissue damage produced by continuous pacing with strong current (40-mA, 4-ms biphasic pulses with 4-Hz frequency for 5 min) on stimulus-generated VEPs and pacing thresholds. A fluorescent optical mapping technique was used to obtain stimulus-induced transmembrane potential distribution around a pacing electrode applied to the ventricular surface of a Langendorff-perfused rabbit heart ( n = 5). Maps and pacing thresholds were recorded before and after tissue damage. Spatial extents of electroporation and cell uncoupling were assessed by propidium iodide ( n = 2) and connexin43 ( n = 3) antibody staining, respectively. On the basis of these data, passive and active three-dimensional bidomain models were built to determine VEP patterns and thresholds for different-sized areas of the damaged region. Electrophysiological results showed that acute tissue damage led to disappearance of the VEP with an associated significant increase in pacing thresholds. Damage was expressed in electroporation and cell uncoupling within a ∼1.0-mm-diameter area around the tip of the electrode. According to computer simulations, cell uncoupling, rather than electroporation, might be the direct cause of VEP elimination and threshold increase, which was nonlinearly dependent on the size of the damaged region. Fiber rotation with depth did not substantially affect the numerical results. The study explains failure to stimulate damaged tissue within the concepts of the VEP theory.

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“…This sustained depolarisation was suspected by Jones et al to be caused by alterations in the electrical properties of the cellular membrane secondary to microbreaks, a phenomenon called "electroporation" [29,30] which can last from a few seconds [30] to minutes [31] according to the model studied.…”

Section: Discussionmentioning

confidence: 93%