Membrane permeabilization and cell damage by ultrashort electric field shocks

Membrane permeabilization and cell damage by ultrashort electric field shocks
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DOI:
10.1016/j.abb.2007.05.003
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发表时间:
2007-09-01
影响因子:
3.9
通讯作者:
Schoenbach, Karl H.
Schoenbach, Karl H.
中科院分区:
生物学3区
文献类型:
--
作者:
Pakhomov, Andrei G.;Shevin, Rachael;Schoenbach, Karl H.

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暴露于纳秒持续时间的电场脉冲(nsPEF; 60 ns,12 kV/cm)的哺乳动物细胞经历了一个深刻的和持久的增加被动电导(G,)的细胞膜,可能是由开放的稳定的电导孔(CP)。CP可渗透Cl-和碱金属阳离子,但不能渗透较大的分子,如碘化丙啶(PI)。CP逐渐重新密封;这个过程需要几分钟,即使在透析细胞和ATP和葡萄糖的溶液中也可以观察到。经历长nsPEF序列(高达200个脉冲)的细胞经历了严重和立即的坏死转化(细胞肿胀、起泡、细胞质颗粒化),但在暴露后至少30-60分钟内保持PI不可渗透。两个G,增加短nsPEF列车和坏死的变化后,长nsPEF列车是细胞类型依赖性的:他们在HeLa细胞比GH 3细胞弱得多。La ~(3+)和Gd ~(3+)离子显著抑制nsPEF诱导的G_1增加(可能是通过阻断CP),并有效地保护强烈暴露的细胞免于发生坏死。我们得出结论,质膜透化是nsPEF暴露细胞坏死转化的主要原因,并可能导致其他已知的nsPEF生物效应。(c)2007年爱思唯尔公司All rights reserved.
Mammalian cells exposed to electric field pulses of nanosecond duration (nsPEF; 60-ns, 12 kV/cm) experienced a profound and long-lasting increase in passive electrical conductance (G,) of the cell membrane, probably caused by opening of stable conductance pores (CPs). The CPs were permeable to Cl- and alkali metal cations, but not to larger molecules such as propidium iodide (PI). CPs gradually resealed; the process took minutes and could be observed even in dialyzed cells and in ATP- and glucose-free solutions. Cells subjected to long nsPEF trains (up to 200 pulses) underwent severe and immediate necrotic transformation (cell swelling, blebbing, cytoplasm granulation), but remained impermeable to PI for at least 30-60 min after the exposure. Both G, increase after short nsPEF trains and necrotic changes after long nsPEF trains were cell type-dependent: they were much weaker in HeLa than in GH3 cells. La3+ and Gd3+ ions significantly inhibited the nsPEF-induced G, increase (probably by blocking the CPs), and effectively protected intensely exposed cells from developing necrosis. We conclude that plasma membrane permeabilization is the principal cause of necrotic transformation in nsPEF-exposed cells and probably contributes to other known nsPEF bioeffects. (c) 2007 Elsevier Inc. All rights reserved.