title: EMF signals and ion/ligand binding kinetics: prediction of bioeffective waveform parameters.
abstract: The kinetics of an electromagnetic field (EMF) target pathway are used to estimate frequency windows for EMF bioeffects. Ion/ligand binding is characterized via first order kinetics from which a specific electrical impedance can be derived. The resistance/capacitance properties of the binding pathway impedance, determined by the kinetics of the rate-determining step, define the frequency range over which the target pathway is most sensitive to external EMF. Applied signals may thus be configured such that their spectral content closely matches that of the target, using evaluation of the signal to thermal noise ratio to optimize waveform parameters. Using the approach proposed in this study, a pulsed radio frequency (PRF) waveform, currently employed clinically for soft tissue repair, was returned by modulation of burst duration, producing significant bioeffects at substantially reduced signal amplitude. Application is made to Ca2+/Calmodulin-dependent myosin phosphorylation, for which the binding time constants may be estimated from reported kinetics, neurite outgrowth from embryonic chick dorsal root explants and bone repair in a fracture model. The results showed that the retuned signal produced increased phosphorylation rates, neurite outgrowth and biomechanical strength that were indistinguishable from those produced by the clinical signal, but with a tenfold reduction in peak signal amplitude, approximately 800-fold reduction in average amplitude and approximately 10(6)-fold reduction in average power.
authors.affiliation: Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Pilla
authors.forename: D J
authors.initials: DJ
authors.lastname: Muehsam
authors.forename: M S
authors.initials: MS
authors.lastname: Markov
authors.forename: B F
authors.initials: BF
authors.lastname: Sisken
mesh_terms: D000465:Algorithms; D000818:Animals; D001846:Bone Development / Q000502:physiology / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002642:Chick Embryo; D004553:Electric Conductivity; D017097:Electric Impedance; D004574:Electromagnetic Fields; D005727:Ganglia, Spinal / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009218:Myosins / Q000378:metabolism; D016501:Neurites / Q000502:physiology / Q000528:radiation effects; D010766:Phosphorylation; D011485:Protein Binding; D011817:Rabbits
chemical_list: D008024:Ligands; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009218:Myosins; D002118:Calcium