Sub-microsecond, intense pulsed electric field applications to cells show specificity of effects

Abstract

Application of sub-microsecond duration (60–300 ns), intense (15–60 kV/cm) pulsed electric fields (sm/i-PEF) to six types of human cells was examined for its effects on individual cell surface membrane permeability and membrane potential. With short (60 ns) pulses, increasing percentages of Jurkat cells showed propidium iodide (PI) uptake at progressively shorter post-pulse times as the pulse train increased from 1 to 10 sequential pulses, while human blood polymorphonuclear leukocytes (PMN) were unresponsive to these short pulses regardless of train size. With 300 ns pulses, a similar pattern (increasing percentages of cells taking up PI, and progressively shorter times of onset after pulse applications as pulse train size increased) was seen with both Jurkat cells and PMN, but the patterns for both effects were different. Jurkat cell size did not appear to influence the responsiveness of this cell type. Comparisons of sm/i-PEF-induced PI uptake by human monocyte-derived macrophages vs. aged human mononuclear cells, human trunk skin (HTS) cells vs. fresh human mononuclear cells and human macrophages vs. HTS cells showed similar overall effects, but with differences between the patterns for each cell type compared (except the macrophages vs. HTS cells comparison). Application of sm/i-PEFs also caused different patterns of membrane potential loss in Jurkat cells vs. PMN. Jurkat cells developed significant decreases in t heir membrane potential only following the highest intensity pulse applications examined, i.e., 300 ns, 60 kV/cm ×5, while PMN showed this effect over the entire range of pulse intensities (300 ns, 15–60 kV/cm, ×5) applied. These data indicate that sm/i-PEF applications can have “specificity” (i.e., achieve different levels of effect in different cell types), that cell size does not appear to be the major factor determining sm/i-PEF effects in either Jurkat cells or PMN, that heterogeneous sm/i-PEF effects on cells tend to become homogeneous with increasing pulse train size, and that specificity of sm/i-PEF applications effects can occur at either end of the sm/i-PEF intensity spectrum examined.