Does electromagnetic therapy meet an equivalent counterpart within the organism?

This review bundles all available new information about intrinsic electrical phenomena in many types of cells (also non-neural) and tissues and shows that exogenously applied electric fields (as DC – EF, EMF or pulsed electromagnetic fields PEMF) can couple to the endogenous electrical phenomena of the body. These endogenous fields are generated ubiquitously in all tissues via cellular ion pumps and transporters and these ion gradients can be transferred by gap junctions. Such electric phenomena can now be monitored in living cells and tissues by electro-sensitive markers. Observations are now available from early embryonic development on to wound healing and regeneration within the adult organism. Based on these grounds we demonstrate that endogenous electric fields act directly on classical pathways of molecular and cell biology. Adequately applied frequencies and pulsing from outside can couple to these endogenous fields or to the receptors of classical biochemical pathways and manifest in positive “reprogramming” of tissue functions. In sum, this new analytical approach to the bodies ́ own electrical information processes opens up new avenues for adequate EMF and PEMF therapy. Introduction In the last decades many clinical studies were published which show beneficial effects of electric field (EF), electromagnetic field (EMF) or pulsed electromagnetic field (PEMF) therapy. If one looks over the vast amounts of publications, it is hard to find a common scientific base for the frequencies, time sequences of applications and intensities used. And often this therapy is questioned in principle because of a supposed lack of an adequate counterpart for EMF therapy from outside. So we address in the present review following questions: 1) Do the EMF/PEMF triggers used in therapy meet an equivalent counterpart in the biological tissue? – Means, are similar electric fields generated endogenously or is no counterpart existing? 2) Which studies in literature show interactions of EMF/PEMF with the “classical” cell biology – and which mechanisms of coupling and which effects show in vitro and in vivo animal experiments as well as clinical studies? Equivalent counterpart in the organism? Elaborated studies could show that electrical and ion gradient phenomena are intrinsic to biological systems. These electric field gradients (“bioelectricity”) are not only created by small ions but are also driven by larger biomolecules. These charge driven electric fields trigger pathways such as cell signaling, tissue factors, growth hormones, transmitters etc [1-7]. Since about ten years from now, new methods like membrane potential– and ion– sensitive in vivo dyes as well as constructs for imaging and molecular tracing are available, allowing a direct observation of the mentioned processes in cells, tissues and living systems. Thus, also effects of electric fields coming from outside as influencing factors to this endogenous bioelectricity and other targets can be studied adequately. In living organisms, electromagnetic fields are generated endogenously mostly as direct current fields (DC) or ultra-low frequency (ULF)-EMF [6]. These fields arise from the segregation of charges by molecular pumps, transporters and ion channels situated in the plasma membrane [8]. Thus, they are not spikes of action potentials like in nerve (required field 10 – 20V/cm) cells but smoothly changing like ULF – EMF. It is important to look first at the resting potential of the cell. Means indeed each type of cell in the body has to maintain it specific level of resting potential at the cell membrane. Differentiated cells possess a high membrane potential with the highest for neurons (-75 mV), glia (-90 mV) and muscle cells (-50 mV). In embryogenesis resting potential values range from -8.5mV in the fertilized egg to -23mV in the fourcell till -25mV in the 16-cell frog embryo [5,9]. It is intriguing that, in general, malignant cancer cells (010 mV) as well as proliferating cells (CHO, 3T3, etc., -12 to -25 mV) have low cell membrane (resting) potentials [10,11]. Recent studies imply that the resting potential is a key regulator of cell cycle as well as of proliferation. Depolarization of cell membrane potential by external changes in ion concentration inhibits G1/S progression of Schwann ́ cells, astrocytes, fibroblasts and lymphocytes. This suggests that hyperpolarization should be important for initiating S – phase [12-14]. Many proteins are involved in this membrane potential triggered cell cycle control [14]. For G2/M transition, depolarization of the plasma membrane should be mandatory. In total *Correspondence to: Richard HW Funk, Institute of Anatomy, Medical Faculty, TU Dresden, Fetscherstr, 74, 01307 Dresden, Germany, Tel: +49 351 4586110; Fax: +49 351 4586103; E-mail: [email protected]