Chapter 7 Interaction of Electromagnetic Field With Cells

In this section we shall discuss have electromagnetic field interacts with cell and sub cellular organ cell, in this section most of the studies done are from invitro studies done one individual cells as it is not possible monitor all the cells in a living organism at a same time. Now we shall split the electromagnetic electromagnetic field into two components i.e. (a) electric field, (b) Magnetic field. The cell membrane blocks the electric component from penetrating the cytoplasma. But magnetic component pass through the cells without any resistance. Before we understand the mechanism by which EMF interacts with cells lets first study the normal structure and function of the cell.

Normal cell structure
An adult human being is made up of approximately 100,000 billion cells. A cell contains many different compartments, organelles, each surrounded by a membrane. The organelles are specialized to carry out different tasks. A large number of proteins carrying out essential functions are constantly being made within our cells. These proteins have to be transported either out of the cell, or to the different compartments - the organelles within the cell, newly synthesized

proteins have an intrinsic signal that is essential for governing them to and across the membrane of the endoplasmic

reticulum,. The cell nucleus contains the genetic material (DNA) and thus governs all functions of the cell. The mitochondria are the "power plants" producing energy needed by the cell, and the endoplasmic reticulum is, together with the ribosomes, responsible for synthesizing proteins, every cell contains approximately one billion protein molecules. The different proteins have a large number of important functions. Some constitute the building blocks for constructing the cell while others function as enzymes catalyzing thousands of specific chemical reactions. The proteins within a cell are constantly degraded and resynthesized.
Figure 1.1 structure of atypical cell

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to a receptor protein in the membrane forms a complex that activates a secondary messenger within the cell to affect a cellular response. inositol phosphate pathway. The first involves activation of cyclic adensosine monophosphate (cAMP) as the secondary messenger. Here I have described these signal mechanisms and the ways in which electric fields may perturb them. Doong et al) Membrane Structure.2 structure of atypical cell membrane showing (from left to right) c AMP pathway. as indicated in Figure 1. 2|P a ge . diacylglycerol. voltage gated ion channels. The attachment of a ligand.2 A pure phospholipid bilayer arrangement is one of the strongest electric insulators known and is therefore quite suitable for maintaining large electrochemical potential gradients at minimal energy expense. The third involves ligand-mediated opening (gating) of ion channels in membrane receptors.Structure of cell membrane Figure 1. Many membrane proteins serve as receptors for external ligands that cannot penetrate to the interior of the cell. In cell membranes. Generally. Some cells have specialized protein channels that allow regulation and selective permeation of ions. cell membranes are thought to be field mosaic composed of large proteins embedded in a thin planar bilayer of aliphatic phospholipids molecules. most ionic current permeates through channels formed by large transmembrane proteins. three different schemes of ligand-mediated signal transduction have been described. Structurally. (Courtesy by lee. and calcium ions. Including inositol triphosphate (IP3). such as a hormone..

the internal calcium concentration can also be raised in response to an external ligand by an increase in flux across the cell membrane. Ligand Gated Channels. In the inositol-membrane lipid pathway. a molecule that regulates many transport and metabolic processes. a phospholipid constituent of the inner membrane. is used as the precursor of the second messengers. activates additional latent proteins to regulate cellular metabolic function. The external concentration of calcium ion is four times greater than 3|P a ge . thereby slowing the production of cAMP. activation of the inhibitory receptor provokes a similar mechanism that results in the inhibition of adenylate cyclase. The Inositol-Membrane Lipid Pathway. Although these schemes are similar across a wide range of cell types. This causes activation of phosphatdylinositol biphosphate on the inner membrane and its hydrolyzation into the secondary messengers IP3 and diacylglycerol.The cAMP Pathweay. IP3 released from the plasma membrane causes the organelles to rapidly release calcium back into the cytosol. Like other cellular organelles. The G3 protein then activates another membrane-bound enzyme. In contrast. phosphatidylinositol4. IP3 is water-soluble and dissolves into the cytosol. to form cAMP. the responses to activation of this pathway vary tremendously. Diacylglycerol molecules diffuse laterally with the membrane. activating the membrane-bound enzyme protein kinase C.5 biphosphate. Protein kinase C. including the activation of calmodulin. CcAMP molecules bind to the regulatory sub-unit of protein kinases within the cell. Both the cAMP and inositollipid pathways use calcium ions as secondary messengers within the cell. cAMP molecules also work by modulating the flow of other secondary messengers such as calcium ions. Besides being released from internal stores such as the endoplasmic reticulum. Activation begins when ligand interaction with a receptor protein signals a ³G´ protein to react with GTP. in turn. adenylate cyclase. It is thought that IP3 acts by stimulating the release of calcium ions from intracellular organelles such as the endoplasmic reticulum. Signal transduction through the cAMP pathway begins with the arrival of an external signal at either a stimulatory or an inhibitory membrane receptor. Activation of the stimulatory receptor molecule signals ³G3´ proteins within the membrane to react with guanine triphosphate (GTP). allowing these enzymes to activated latent proteins by phosphorylation to perform a genetically programmed fundion. Increased cytoplasmic free calcium has many known effects.

two distinct voltage-gated calcium ion channels in non excitable cells have been discovered. Compared with electrically excitable cells like nerve and muscle. relatively few calcium channels exist in non excitable cells such as blood cells and bone cells. There are four reasons for this notion. As an example. One type is activated by a change in transmembrane potential from -30 mV to 20 mV. Hence in following section we will discuss the effects of electric field and magnetic field differently even though they are two sides of a same coin. Dose of electric field 4|P a ge . many ion channels are sensitive to the strength of the transmembrane potential changes in the voltage across the membrane. maintaining a potential gradient of almost 100 mV across the membrane through ion pumps. In addition to ligand-gates channels. Cell membrane is considered to be the main site where the electric field interacts with the cell.. These channels are the most direct membrane-bound electrochemical transducers. 40 mV to 50 mV) are required to significantly alter calcium ion flux.e. Changes in the voltage across the membrane directly turn the channel on and off. Mechanism of electric field interaction with cell membrane. c) Changes in the ion flow across the membrane especially calcium ion have been reported in many EMF studies. and the regulation of specific ion channels permits the careful control of calcium influx. the binding of parathyroid hormone (PTH) is accompanied by an increase in calcium influx. Important Note:Cell membrane does not permit the electric field to enter into the cytoplasm hence the electric field acts on the cell via membrane channels and proteins to bring changes inside the cell.internal levels. a) An applied electric field is amplified within the cell membrane. However. The magnetic field can pass through the cell without any resistance it directly acts on the intra cellular molecules and organellae to bring about the changes. d) Membrane itself is involved in controlling the electrical aspects of the cell. b) The cell membrane is major transduction pathway as many ligand gated channels and voltage gated channels are located in it. Relatively large changes in transmembrane potential (i.

Doong et al).3 below. In cell cultures it is observed that cell which are placed parallel to the electric field are more sensitive to applied electric field than cells which are perpendicular to the electric field. 5|P a ge 7 . this is because when the cells are placed parallel to the electric field the electric fiels is distributed equallt around the cell as shown in the figure 1.e if 1 Volt is applied only 1mV enters the cytoplasma1. Only less than 1% electric field penetrates anterior of the cell i.3 schematic diagram showing distribution of electric field around the cell placed parallel to the electric field (Eo) (Courtesy by lee. in a typical mammalian cell a electric field signal of 20-5-mV/cm2 is must to stimulate cell membrane3-5 Field Interaction Mechanisms One possible method of electrochemical transduction involves the ability of applied fields to alter the density and distribution of charged cell-surface proteins6. As we know there is lot of electrochemical activity is going on in a cell. Because of this. Several binding interactions between physiologic ligands and cell-surface receptors have been shown to obey second-order reversible binding kinetics.e.Cell membrane has a high dielectric constant it behaves as a good insulator for electric field. This receptor redistribution would directly perturb the cAMP and IP3 mechanisms described above by acting on the ligand-receptor bidning kinetics . figure 1. the applied field must overcome this background noise i.2. it is likely that ligand-receptor binding can be regulated by redistribution and local concentration of surface receptors. signal to noise ratio should be greater then (one) 1. The conductivity of cell membrane is 10-6 times lesser than the conductivity of the plasma.

6|P a ge .. however. mechanical rectification of electrophoretic movement may result.. between the magnitude or duration of calcium change and the magnitude or duration of the cellular response15. with the most rapid diffusion occurring in the direction parallel to the underlying actin stress fibers. Stolpen et al. Calcium ions mediate the action of many other epigenetic regulatory signals and are known as one of the universal second messengers14. demonstrated that succinyl concanavalinA receptors diffuse anisotropically on murine fibroblasts10.9. In some cells the magnitude of the response is related to the magnitude of the change in cytoplasmic calcium (eg. skeletal muscle contraction). if resistance-to-receptor movement in the plane of the cell membrane is anisotropic. electric fields could in theory indirectly regulate intracellular calcium transport68.g. the expected distance traveled in half a cycle by a single-membrane-imbedded concanavalin A receptor with ³effective´ electrophoretic mobility of ~2x10-7 cm2/V-sec is less than 1 A0 Although this distance is negligible compared with Brownian motion. using a ³video-FRAP´ (Fluorescent Recovery After Photo bleaching) technique. Calcium Modulated Effects. In 1978 Smith et al.. Because hormone-receptor binding also regulates Trans membrane ion fluxes. using a new technique called ³line FRAP. Recently. This has been most clearly shown to occur in calcium-dependent galvanotaxis13.In an oscillating electrical field of 1 V/cm and a frequency of 1 Hz. smooth-muscle constriction. Receptor crowding toward one part of the cell may occur and may change the probability of ligand binding or dissociation. insulin secretion) exhibit no simple corleation. including fibroblasts. Cells in which the response to calcium is prolonged (e.: observed that human dermal fibroblasts exhibit anisotropic diffusion of fluorescence recovery in class I major histocompatibility complex proteins but that human vascular endothelial cells do not exhibit this diffusion12. Kaptza et al. Controversy still exists regarding the existence of this mechanism in different cell types. Established evidence exists for anisotropic resistance to movement along certain cells. observed that concanavalinA receptor diffusion on human foreskin fibroblasts is independent of direction11. Many studies implicate intracellular calcium fluxes as an intermediate in EMF stimulation of cellular response. Rectification would lead to a net lateral displacement of the receptor over many cycles. The complexity of the calcium messenger system varies from one cell to another.

The migration of fibroblasts into the wound during the healing process is probably related to a 90 Kd protein.. field-imposed variations might similarly modulte cellular behavior . proliferation. yet any alteration in the transport of calcium ion channels might shift the frequency of these oscillations and provide a signal to the cell. One role of calcium in biosynthesis involves exocytosis of procollagen into the extracellular matrix. 7|P a ge . found that 20 V/cm electric field exposure increases Na+ Ca2+ transport activity in plant protoplasts in a frequency-dependent manner. Changing intracellular calcium concentration has profound effects on cell migration. which then increases Na+ Ca2+ membrane transport16. Imposed transmembrane potentials are small. and the synthesis of tissue components. it breaks up the cross-linked network of actin filaments within the cell and makes the cell more fluid and mobile. has demonstrated the influence of electric fields on the membrane bound calcium ATPase pumps that maintain the large calcium gradient inside the cell. Grazana et al. geloslin. Blocking calcium ion flow into the cell may interrupt the secretion of cell matrix constituents and may therefore inhibit the formation of tissue collagen.Recent work by Grazians et al.. gelsolin may help the overall migration of fibroblasts17. The modulation of calcium concentration may therefore provide the mechanisms by which electric fields effect the synthesis of extracellular tissue products18. Experiments by Kelly and others have shown that exocytosis is a calcium-dependent process. Because IP3 release can be triggered by elevated free calcium in the cytoplasm a feedback loop may exist that can drive large oscillations in cytoplasmic free calcium ion concentration. By alternately breaking and reassembling the filaments of cytoskeleton. These calcium oscillations may contain a transmembrane ion flux component sensitive to electric field changes in ion transport. indicating that the oscillation frequency itself may act as a secondary signal for mediating cellular activity20. When gelsolin is activated by the binding of calcium ions. They attribute this change to an indirect mechanism in which electric field stimulation of membrane-bound ATPsynthase and increases the intracellular concentration of ATP. Because variations in oscillation frequency have been linked to ligand in terection at the membrane. Berridge and Galione recently reported that the oscillation frequency appears to be cell-type specific and seems to vary with the presence of external ligands.

(Courtesy by lee. now place a strong magnet near the jar after some time the iron pins will be collected towards the side of magnet. flow across the membrane. Doong et al).4 schematic diagram of effect of electric field on the membrane receptors. this is what exactly happens to receptors and this is called anisotropic property. arrows show the direction of electric field (Courtesy by lee.5 shows displacement of membrane proteins along the direction of the electric field. Figure 1. Doong et al). now place butter in a jar and place the iron pins above its surface this is analogous to the cellmembrane with receptosa.Metaphore illustration Compare the lipid bilayer if the csll membrane with butter. due to this movement channels open and ions Figure 1. note that with each pule or wave of electric field more number of transmembrane proteins displaced increases. compare the transmembrane receptors to emall iron pins with cap. 8|P a ge .

Cyclotron resonance is one mechanism proposed to explain the experimentally observed interaction of electric and magnetic fields are applied that corresponds to the natural resonant frequency of the ion. in the following section we have covered only those phenomenon which are supported by a good amount of scientific evidence. A new theory proposed by Blank and Goodman suggests that counter ion migration away from the equilibrium position around charged intracellular proteins may result from applied electrical fields. Downregulate dysregulatory and apoptotic gene loci. Mechanism of magnetic field interaction with cell Cellular responses to magnetic fields are even more complex and difficult to understand because the field penetrates the cell uniformly. 1. Cytosolic ± Calcium The magnetic field increases the free energy or entropy of the intracellular organellae cells preview this as homeostatic challenge and cellular response to homeostatic challenge is the release of calcium from intracellular stores that prompts mitochondria to produce free radicals 9|P a ge .24. As evidence. it is beyond the scope of this book to explain all the effects. This energetic response includes absorbing sufficient velocity to traverse a membrane channel more easily.Other Mechanisms Some other less accepted theories are available which attempts to explain effect of electric field on the cell membrane. the major phenomenon are. Restore equilibrium in ROS (free radical)/antioxidant chemistry 3. Stabilize cytosolic Calcium 2. the authors cite changes in applied magnetic fields that have been observed to shift the frequency window of cell sensitivity to applied electric fields23. This theory predicts the frequency dependence of biosynthetic response that has been reported21. 1. Magnetic field in living tissues effects directly and/or induces electrical currents that interacts with the cell and its organellae to bring about the biological response. The exposed fixed charges on the protein could alter protein conformation and result in altered mRNA transcription or translation.22. Upregulate classes of protective and restorative gene loci 4.

In the NASA study some 13. Downregulate dysregulatory genes.000 gene loci responses to square wave with rapid dB/dt pulse characteristics were studied with two software programs at an n¼96. this knowledge may pose interesting possibilities when cancer mitigation becomes part of this technology33. Stabilized free radical chemistry. 3. Cytoprotective genes come in to play when there is challenge to the survival of the cell.000 were down regulated representing dysregulatory loci. Free radicals of oxygen are paramagnetic in nature and they exhibit dipole alignment when exposed to a magnetic field. this makes the anti oxidant machinery to detect the free radical very easy. transplant survival. bone graft survival. due to this when a magnetic field is applied to the cell as the free radicals carry a negative charge they exhibit dipole alignment and become stabilized in one position.000 loci were upregulated that represented classes of restorative genes.(in physiological limit) and heightens DNA response which eventually leads to protein synthesis25. Upregulation of cytoprotective and restoration genes. 2.000 loci were unaffected. and 8.28. ischemic injury and so on whenever such threat is detected the cytoprotective genes are activated. 10 | P a g e .26. 2. for example reperfusion injury. The latter were reported as µµhouse-keeping¶¶ loci and µµother closely conserved sites. 60 Hz frequency for 20 minutes (in invitro setting) upregulates HSP70 gene and decreases cell mortality by 80%. It found that 3. thus antioxidation process is facilitated27. which is of great therapeutic significance29-32. application of magnetic field of 8 micro T. one of the most important cytoprotective gene is HSP 70.¶¶ This also seems a logical phenomenology among living systems to achieve homeostasis.

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