Activation-dependent and biphasic electromagnetic field effects: model based on cooperative enzyme kinetics in cellular signaling.

Experiments on filed exposure effects of extremely-low-frequency electric and magnetic fields (EMFs) on biological systems have shown that, in many cases, the biological-functional status is of fundamental importance for an effective interaction. For example, studies of calcium uptake regulation in cells of the immune system, particularly in T lymphocytes, have revealed that, depending on the degree of cellular activation, either stimulatory, inhibitory, or no field exposure effects are observed for identical field parameters. A brief summary of the experimental findings is given, and a theoretical approach is presented that accounts in a qualitative manner for EMF exposure effects 1) that depend on the degree of cellular activation and 2) that exhibit a biphasic response behavior (stimulation/ inhibition). In the model, biochemical stimulation of the cell results in activation of specific signaling pathways that regulate calcium dynamics in the cell (calcium release from intracellular calcium stores and capacitative calcium entry). We assume that, controlled by these pathways, a specific EMF-sensitive enzyme system becomes activated. The activated enzyme, in turn, exhibits a feedback control on the signal processes, thus leading to a modulation of calcium entry. This modulation may affect other cellular processes that are calcium dependent (e.g., DNA synthesis). Magnetic field exposure is assumed to alter the kinetics of a specific step within the enzyme-reaction cycle in accord with the radical-pair mechanism, although the formulism is not restricted to this specific example. Results show that inclusion of cooperative steps within the enzyme-reaction cycle provides a theoretical basis that enables a simple description of a biphasic response behavior to EMF exposure.