title: Considering effects of nanosecond pulsed electric fields on proteins.
abstract: Most, if not all, effects of intense, pulsed electric fields are analyzed in terms of electrical charging of plasma membranes and/or subcellular membranes. However, not all cell responses from nanosecond pulsed electric fields (nsPEFs) are fully explained by poration of cell membranes. Observations that nsPEFs induce a Ca2-dependent dissipation of the mitochondria membrane potential (ΔΨm), which is enhanced when high frequency components are present in fast rise-fall waveforms, are not compatible with a poration event. Ca(2+) is shown to have little or no effect on propidium iodide uptake as a measure of plasma membrane poration and consequently intracellular membranes. Since most if not all Ca(2+)-regulated events are mediated by proteins, actions of nsPEFs on a protein(s) that regulate and/or affect the mitochondria membrane potential are possible. To show that nsPEFs can directly affect proteins, nsPEFs non-thermally inactivated the catalytic (phosphotransferase) activity of the catalytic subunit of the cAMP-dependent protein kinase, which is the prototype of the protein kinase superfamily that share a common catalytic mechanism and whose functions are highly dependent on their structure. These studies present indirect and direct evidences that nsPEFs can affect proteins and their functions, at least in part, by affecting their structure.
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA 23508, United States. Electronic address: sbeebe@odu.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Beebe
mesh_terms: D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000737:chemistry / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism
chemical_list: D011506:Proteins; D016572:Cyclosporine; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C463959:protein kinase A Calpha; D002118:Calcium
keywords: Calcium; Electric fields; Mitochondria membrane potential; Molecular dynamics; cAMP-dependent protein kinase