Nanosecond pulsed electric fields mimic natural cell signal transduction mechanisms

Applications of nanosecond pulsed electric fields (nsPEF) to human cells and mammalian tissues indicate that, as the pulse durations and/or the electric field intensities decrease, effects on the plasma membrane decrease and effects in intracellular signal transduction mechanisms increase. NsPEFs that are below the threshold for electroporation-like effects on the plasma membrane mimic cell-signaling mechanisms that determine cell fate, depending on the nsPEF conditions and the cell type. At relatively high electric fields, cell-signaling mechanisms are activated to induce death by apoptosis in cells and tumors. At electric fields below the threshold for apoptosis, nsPEFs induce calcium release from intracellular stores that mimic physiologic ligand effects on IP3-dependent calcium channels in the endoplasmic reticulum and subsequent capacitative calcium influx activated by store operated calcium channels (SOCC) in plasma membranes. In human platelets, nsPEF-induced calcium mobilization mimics thrombin-induced platelet activation and aggregation, a natural mechanism to clot blood and heal wounds. Thus, nsPEFs recruit intracellular signaling mechanisms, providing a new technology to modulate cell function for potential therapeutic and/or diagnostic applications in the future.