Article

Recruitment of the intracellular Ca2+ by ultrashort electric stimuli: The impact of pulse duration

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA. Electronic address: .
Cell calcium (Impact Factor: 4.21). 06/2013; 54(3). DOI: 10.1016/j.ceca.2013.05.008
Source: PubMed

ABSTRACT Nanosecond-duration electric stimuli are distinguished by the ability to permeabilize intracellular membranes and recruit Ca(2+) from intracellular stores. We quantified this effect in non-excitable cells (CHO) using ratiometric Ca(2+) imaging with Fura-2. In a Ca(2+)-free medium, 10-, 60-, and 300-ns stimuli evoked Ca(2+) transients by mobilization of Ca(2+) from the endoplasmic reticulum. With 2mM external Ca(2+), the transients included both extra- and intracellular components. The recruitment of intracellular Ca(2+) increased as the stimulus duration decreased. At the threshold of 200-300nM, the transients were amplified by calcium-induced calcium release. We conclude that nanosecond stimuli mimic Ca(2+) signaling while bypassing the usual receptor- and channels-mediated cascades. The recruitment of the intracellular Ca(2+) can be controlled by the duration of the stimulus.

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    • "Caution was exercised not to assume that nsPEFs mimicked plasma membrane electroporation by permeabilizing intracellular membranes. Effects on these vesicles [2] and release of Ca 2+ from intracellular stores [3] [4] [5] [6] [7] or α-granules [8] could be readily explained by permeabilization or electroporation events. However, for the most part, these are assumptions that extend from conventional electroporation effects on plasma membranes. "
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    Bioelectrochemistry 08/2014; 103. DOI:10.1016/j.bioelechem.2014.08.014 · 3.87 Impact Factor
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    • "These findings were corroborated using both patch clamp and fluorescence microscopy, leading to the conclusion that nsPEF caused nanoporation (formation of nanometer diameter pores) in the plasma membrane [12] [13]. Recent publications have also shown that this " nanopermeabilization, " by allowing the rapid uptake of calcium, activates intracellular signaling pathways and calcium-induced-calcium uptake [14] [15] [16]. The activation of these processes and elevated intracellular calcium concentration can in itself lead to intrinsic apoptosis, mitochondrial depolarization and damage, making the original observations of field-induced intracellular effects of nsPEF suspect. "
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