These models explain biological processes considering electromagnetic fields as modulators of molecular information transfer. It is considered that the EMF either itself acts as signal(s) and/or intercepts or modifies the processes of molecular interaction.

6.4.2.1 ION CYCLOTRON RESONANCE CONCEPT

Many authors have developed the idea of ion cyclotron resonance (ICR) of specific ions like Ca2+ and Na+ [68] which predicts ELF magnetic effects at the cyclotron frequencies and there harmonics. Later, it was modified to the ion parametric resonance (IPR) model, which includes the cyclotron sub harmonics. The IPR is composed of a number of theoretical models based on classical and quantum electrodynamics where biomagnetic ef­fects are considered as magnetically modulated ion binding in ion-ligand interactions [69]. Free ions move with the cyclotron frequency in a static magnetic field and can be influenced by ELF magnetic fields or appropri­ate frequencies [70]. The main focus of these studies was the essential role of Ca2+ ions in magnetobiology experiments. It is proposed that ion behav­ior in channels like the acetylcholine receptor have constrictions in them, which cause thermal collisions. Under certain magnetic field parameters the wall collisions could be avoided at certain amplitudes and frequencies determined for the Lorentz force equation [71]. Under these conditions, the ions are predicted to “fly” through the channel unimpeded increasing the membrane permeability. ICR allows circulation of ions through selec­tive enhancement, which affects the rate of biochemical reactions [72].

The fact that magnetic fields can modulate enzyme activities in vitro is a crucial observation, because it indicates that enzymes may function as magnetoreceptors [69]. EMF modulations could also initiate changes in the distribution of protein and lipid domains in the membrane bilayer, as well as conformational changes in lipid-protein associations [1]. The interface between cell membrane and extra and intercellular fluids can be electrified on the order of 106 to 1010 V cm-1 [73]. The impact of an elec­tric field on a biological cell membrane and its change with time may constitute a relevant mechanism of information transmission influencing the membrane properties. The electric field, mainly generated by ions flowing to the membrane from the external environment, can change the molecular distribution of electronic charge inside each lipid molecule, producing perturbations of collective excitations in the mechanical and electrical properties of the lipid chain which can be treated as a mechanism for intermembrane communication, analogous to a damped harmonic os­cillations [74].

Pilla et al. [73] presented a working model of electrochemical informa­tion transfer by which the injection of low-level current can provide func­tional selectivity in the kinetic modulation of cell regulation. His theory was based on ion/ligand binding being a possible transduction mechanism for the detection of exogenous EMF’s at the cell membrane [75]. In or­der to derive the specifications for electromagnetic field signals having optimal biological effects, it is first necessary to develop a model for the underlying biological processes which are assumed to be complex physi­cal systems that may be modeled mathematically as non-linear, time-vary­ing, finite-dimensional dynamic systems. They developed a method for the systematic analysis of electrical impedance for each relevant electro­chemical pathway of a cellular system [62]. The electrochemical transfer hypothesis postulated that the cell membrane would be the site of interac­tion of low level electromagnetic fields by altering the rate of binding of calcium ions to enzymes or receptor sites [1]. The Ca2+ pathway can be influenced by EMFs on the complex chain of transduction, amplification, and expression.

Experimental results have shown that specific ion/ligand binding path­ways such as Ca2+ binding to calmodulin (CaM) and the ensuing steps of calcium-dependent signaling to intracellular enzymes may act as primary transduction mechanisms for EMF detection leading to an increase in the instantaneous reaction velocity and enzyme kinetics [75,76]. Calmodulin also plays a role in many other important biochemical processes such as cell proliferation, Ca2+ membrane transport and plant cell function [77]. An alteration of cell signaling events can lead to changes in cell prolifera­tion and differentiation, which can be initiated, promoted or co-promoted [70]. The capability of the weak EMF to have a bioeffect appears to reside in the informational content of the waveform [1]. The waveform duration and the voltage dependence are the most important parameters to increase the activity of the specific adsorption of an enzyme [62]. The proposed interfacial membrane model reveals that it is entirely reasonable to expect specific electrochemical effects as a result of electrical stimulation with signals of relatively low frequency and amplitude [73].

The incorporation of quantum states into ion interference has also been involved in the explanation of the physical nature of magnetoreception [78]. Variations in magnetic field magnitude affect the phase of ion wave functions and the interference of these phase changes affect the physi­cal observables in quantum mechanics. This theory predicts magnetobio­logical effects for magnitude/direction modulated magnetic fields, pulsed magnetic fields and weak AC electric fields among others [51]. In these cases, ions of calcium, magnesium, zinc, hydrogen, and potassium appear to be relevant. However, the most prominent example of a proven bio­electromagnetic mechanism is the radical pair recombination mechanism, which has been demonstrated biochemically in vitro. Radical pairs are formed as reaction intermediates in many biochemical reactions within complex reaction chains under the influence of exogenous electromag­netic influence [70]. The recent breakthrough regarding the radical pair mechanism in the blue light receptor protein, cryptochrome, by Schulten and his colleagues, supports the concept that radical pair recombination is involved in magnetoreception in avian navigation. Molecular model­ing and calculations showed that the signaling of cryptochrome, which involves a photoreduction process, can be modulated in the presence of a magnetic field on the order of 1 mT inducing an increase in the signal­ing activity of the protein by ~10% [79,80]. This prediction appears to be consistent with the experimental results on the effect of magnetic fields on cryptochrome-dependent responses in Arabidopsis thaliana seedlings attained by Ahmad and coworkers [81]. It is then suggested that the mag­netic navigation capability could be mediated by the presence of cryp­tochrome that is localized in the retinas of migratory birds which could alter how the bird perceives colors enabling something akin to an internal magnetic compass [82]. This radical pair mechanism is probably coupled with the alternative magnetite-based mechanism of magnetoreception and navigation, which poses that the Earth’s magnetic field exerts a minute mechanical force on the magnetite particles found in the upper beaks of migrating birds providing positional information due to fluctuations in the geomagnetic strength in different locations [83].