Arthur D. Rosen

Mechanism of action of moderate-intensity static magnetic fields on biological systems

There is substantial evidence indicating that moderate-intensity static magnetic fields (SMF) are capable of influencing a number of biological systems, particularly those whose function is closely linked to the properties of membrane channels. Most of the reported moderate SMF effects may be explained on the basis of alterations in membrane calcium ion flux. The mechanism suggested to explain these effects is based on the diamagnetic anisitropic properties of membrane phospholipids. It is proposed that reorientation of these molecules during moderate SMF exposure will result in the deformation of imbedded ion channels, thereby altering their activation kinetics. Channel inactivation would not be expected to be influenced by these fields because this mechanism is not located within the intramembraneous portion of the channel. Patch-clamp studies of calcium channels have provided support for this hypothesis, as well as demonstrating a temperature dependency that is understandable on the basis of the membrane thermotropic phase transition. Additional studies have demonstrated that sodium channels are similarly affected by SMFs, although to a lesser degree. These findings support the view that moderate SMF effects on biological membranes represent a general phenomenon, with some channels being more susceptible than others to membrane deformation.

Inhibition of calcium channel activation in GH3 cells by static magnetic fields.

Voltage-activated calcium channel function was examined in cultured GH3 cells using the whole-cell patch clamp technique. Exposure to a 120 mT static magnetic field resulted in a slight reduction in the peak calcium current amplitude and shift in the current-voltage relationship. The most significant change was a slowing of the channel activation rate without any change in the inactivation rate. All changes in channel function were reversible, with return to pre-exposure values within 3 min after the field was turned off. These alterations in channel function were temperature-dependent. The present findings are consistent with a functional disruption of the intramembranous portion of the calcium channel by a magnetically induced membrane deformation.

Focal epileptogenesis after intracortical hemoglobin injection.

Abstract Intracortical injection of purified bovine hemoglobin produced chronic focal spike activity in 89% of rats tested; 50% of the animals evidenced spike activity within 48 h. The lesions produced were pathologically similar to those seen in post-traumatic epilepsy. Evidence is presented suggesting that the neural effect of iron released from hemoglobin may be causally related to the development of a trauma-induced epileptiform focus in humans.

Magnetic field influence on central nervous system function

The effects of strong static magnetic fields on the excitability of striate cortex in adult cats was studied. The visual evoked response was used as a measure of cortical excitability. In all animals a 1200-G field was associated with a significant decrease in both amplitude and variability of the evoked response. This effect began more than 50 s after the field was turned on and persisted, even after the field was turned off, for several minutes. This phenomenon appears to be due to action of the magnetic field at the synapse rather than on axonal conduction.

Membrane response to static magnetic fields: effect of exposure duration

The time-course for the reversible alteration in presynaptic membrane function associated with exposure to a 123 mT static magnetic field was examined in an attempt to help define the mechanism whereby these fields influence biomembranes. Miniature endplate potentials (MEPPs) were recorded in the isolated murine neuromuscular junction preparation, maintained at a temperature of 35.5 degrees C. A minimum field duration of 50 s was found to be necessary for MEPP inhibition, with the efficacy of the field in inducing further inhibition being a function of its duration, but only for periods up to 150 s. Longer durations were not associated with additional inhibition. The time required for MEPP frequency to return to baseline, following deactivation of the field, was found to be linear for field durations up to 150 s. At and above this limit, recovery time remained constant at 135 s. These findings are consistent with the slow reorientation of diamagnetic molecular domains within the membrane and suggest tight coupling to the mechanism responsible for neurotransmitter release. The limits on this effect are compatible with the mechanical constraints imposed by the membranes cytoskeleton.

Modification of spontaneous unit discharge in the lateral geniculate body by a magnetic field

The effects of a 1230-G static magnetic field on spontaneous discharge frequency and discharge pattern of principle cells in the cats lateral geniculate body (LGB) were examined. In 45% of cells studied, a decrease in frequency was seen after the field was turned on. This progressed, even after the field was turned off, with return to baseline after an average duration of 250 s. Onset typically was 75 s after the field was activated, with maximum effect occurring 135 sec thereafter. In 67% of those cells which exhibited a decrease in frequency and in 50% of those which did not, a change in discharge pattern, as reflected by the interspike interval histogram, was seen. When present, this was manifested as a decrease in short interspike intervals. The change in the interspike interval histogram usually persisted longer than the change in frequency. The gradual onset and prolonged time course of changes in LGB cell activity suggest either an alteration in the synaptic ionic environment or in neurotransmitter availability. It is hypothesized that strong magnetic fields produce a partial realignment of diamagnetically anisotropic molecules within the cell membrane, thereby distorting ion-specific channels sufficiently to alter their function.

Effect of a 0.5-T static magnetic field on conduction in guinea pig spinal cord.

Compound-evoked potentials were recorded from excised adult guinea pig spinal cords before, during, and following exposure to a 0.5-T static magnetic field (SMF). There was no change in response latency during exposure but there was a small, statistically significant, decrease in amplitude. Maximum effect was evident 1 to 2 min after the field was turned on with return to baseline within 1 min after the field was turned off. These results may be explained by a conduction block in the small axon subpopulation due to the effect of static magnetic fields on voltage-activated sodium channels. The relative selectivity of the field is believed to occur because of the relatively greater number of sodium channels present in smaller axons.

Nonlinear temperature modulation of sodium channel kinetics in GH3 cells

The effect of temperature on sodium channel function was examined in GH(3) cells, using the whole cell patch-clamp methodology. Specific parameters examined were current-voltage relationships, activation time, and inactivation time. For the temperature range studied, 23-37 degrees C, there was no change in the current-voltage relationship. A linear response to temperature was seen in the inactivation time constant, tau(h). The activation time constant, tau(m), was clearly nonlinear, with a sharp discontinuity at 28 degrees C. This nonlinearity was especially evident at lower membrane voltages. These findings are consistent with the hypothesis that membrane structural changes, which occur during the thermotropic phase transition, are capable of influencing the function of the intramembranous portion of the channel. Caution should, therefore, be exercised in extrapolating data on channel function obtained at room temperature to physiological temperatures.

Magnetic field influence on paramecium motility.

The influence of a moderately intense static magnetic field on movement patterns of free swimming Paramecium was studied. When exposed to fields of 0.126 T, these ciliated protozoa exhibited significant reduction in velocity as well as a disorganization of movement pattern. It is suggested that these findings may be explained on the basis of alteration in function of ion specific channels within the cell membrane.

Visual radiation activity during a cortical penicillin discharge

The electrical behavior of 274 principal cells of the dorsal nucleus of the lateral geniculate body of cat has been studied during the discharge of a penicillin focus in the primary visual cortex. In 17% of the cells, spike activity was observed during the penicillin discharge. The activity consisted of 1–40 spikes at frequencies as high as 500/sec. When the penicillin discharge initiated a prolonged seizure, activity in the principal cells continued throughout the seizures at rates from 100–200/sec. The temporal properties of the activity and the detailed structure of single spikes studied with glass microelectrodes in the geniculate suggest that this activity is antidromic. Stimulation of the visual radiation at its origin in the geniculate at various times during a penicillin discharge revealed marked reduction in amplitude of the population response recorded at the terminus of the radiation in the cortex. The degree of reduction followed approximately the time course of the penicillin discharge and was great enough to suggest two additive etiologies, viz., refractoriness or occlusion during the penicillin discharge and depolarization of the radiation fiber terminals.