Effects of usEPs on Plasma Membranes—Pores, Channels, and Repair

Receptors, channels, glycoprotein, and transport proteins, among other integral proteins, load the plasma membrane lipid bilayer, which receives reinforcement from cytoskeletal filaments as the boundaries of cellular life. Early studies suggested that usEPs did not induce plasma membrane permeabilization until relatively high amplitude conditions. As will be discussed here and elsewhere, this was because the usEP-induced plasma membrane pores were so small that they did not allow entry of propidium iodide, a commonly used marker for permeability, or calcein exit from the cell. The plasma membrane contained nanoelectropores or nanopores, so-called because they were ~1 nm in diameter. These lipid nanopore structures exhibited complex conductances similar to classic pores, which are common in protein structures. Another finding presented some confounding information regarding plasma membrane phosphatidylserine (PS) externalization, commonly used as a marker for apoptosis. usEPs “pulled” PS through these nanopores. Now PS externalization was an ambiguous marker for apoptosis. Although plasma membrane lipids were clear usEP targets, plasma membrane channels were also targets for usEPs. As will be discussed, these effects could be due indirectly to nanopore formation or possibly directly on the channels themselves, although more evidence for direct effects is necessary. In any event, patch-clamp techniques provided new, exciting, and valuable information about usEP effects on plasma membranes. As might be expected, cells have mechanisms that confront nanopore formation and other possible usEP-induced injuries, which will be presented. Finally, in relatively uncharted territory, usEPs were also shown to affect redox systems in plasma membranes as electron carriers. Although usEPs are unique for their effects on intracellular structures and functions, their impact on the plasma membrane has provided a wealth of information about how they can be used as tools in biology and medicine.