Neuronal Effects

J Neural Eng. 2010 Aug;7(4):045003. Epub 2010 Jul 19.

Modulation of neuronal activity and plasma membrane properties with low-power millimeter waves in organotypic cortical slices.

Pikov V, Arakaki X, Harrington M, Fraser SE, Siegel PH.

Neural Engineering Program, Huntington Medial Research Institutes, Pasadena, CA, USA. pikov@hotmail.com

Abstract

As millimeter waves (MMWs) are being increasingly used in communications and military applications, their potential effects on biological tissue has become an important issue for scientific inquiry. Specifically, several MMW effects on the whole-nerve activity were reported, but the underlying neuronal changes remain unexplored. This study used slices of cortical tissue to evaluate the MMW effects on individual pyramidal neurons under conditions mimicking their in vivo environment. The applied levels of MMW power are three orders of magnitude below the existing safe limit for human exposure of 1 mW cm(-2). Surprisingly, even at these low power levels, MMWs were able to produce considerable changes in neuronal firing rate and plasma membrane properties. At the power density approaching 1 microW cm(-2), 1 min of MMW exposure reduced the firing rate to one third of the pre-exposure level in four out of eight examined neurons. The width of the action potentials was narrowed by MMW exposure to 17% of the baseline value and the membrane input resistance decreased to 54% of the baseline value across all neurons. These effects were short lasting (2 min or less) and were accompanied by MMW-induced heating of the bath solution at 3 degrees C. Comparison of these results with previously published data on the effects of general bath heating of 10 degrees C indicated that MMW-induced effects cannot be fully attributed to heating and may involve specific MMW absorption by the tissue. Blocking of the intracellular Ca(2+)-mediated signaling did not significantly alter the MMW-induced neuronal responses suggesting that MMWs interacted directly with the neuronal plasma membrane. The presented results constitute the first demonstration of direct real-time monitoring of the impact of MMWs on nervous tissue at a microscopic scale. Implication of these findings for the therapeutic modulation of neuronal excitability is discussed.

Bioelectromagnetics. 2010 Apr;31(3):180-90.

Millimeter wave effects on electrical responses of the sural nerve in vivo.

Alekseev SI, Gordiienko OV, Radzievsky AA, Ziskin MC.

Center for Biomedical Physics, Temple University Medical School, 3400 N. Broad Street, Philadelphia, PA 19140, USA.

Abstract

Millimeter wave (MMW, 42.25 GHz)-induced changes in electrical activity of the murine sural nerve were studied in vivo using external electrode recordings. MMW were applied to the receptive field of the sural nerve in the hind paw. We found two types of responses of the sural nerve to MMW exposure. First, MMW exposure at the incident power density >/=45 mW/cm(2) inhibited the spontaneous electrical activity. Exposure with lower intensities (10-30 mW/cm(2)) produced no detectable changes in the firing rate. Second, the nerve responded to the cessation of MMW exposure with a transient increase in the firing rate. The effect lasted 20-40 s. The threshold intensity for this effect was 160 mW/cm(2). Radiant heat exposure reproduced only the inhibitory effect of MMW but not the transient excitatory response. Depletion of mast cells by compound 48/80 eliminated the transient response of the nerve. It was suggested that the cold sensitive fibers were responsible for the inhibitory effect of MMW and radiant heat exposures. However, the receptors and mechanisms involved in inducing the transient response to MMW exposure are not clear. The hypothesis of mast cell involvement was discussed.

Radiat Res. 2009 Dec;172(6):725-36.

Altered calcium dynamics mediates P19-derived neuron-like cell responses to millimeter-wave radiation.

Titushkin IA, Rao VS, Pickard WF, Moros EG, Shafirstein G, Cho MR.

Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan Street, Chicago, IL 60607, USA.

Abstract

Intracellular calcium oscillations have long been recognized as a principal mediator of many vital cellular activities. Furthermore, Ca(2+) dynamics can be modulated by external physical cues, including electromagnetic fields. While cellular responses to low-frequency electric fields have been established, the possible non-thermal effects of millimeter-wave (MMW) radiation are still a subject of discussion and debate. We used mouse embryonic stem cell-derived neuronal cells and a custom-built 94 GHz applicator to examine in real time the altered Ca(2+) oscillations associated with MMW stimulation. MMW irradiation at 18.6 kW/m(2) nominal power density significantly increased the Ca(2+) spiking frequency in the cells exhibiting Ca(2+) activity. The N-type calcium channels, phospholipase C enzyme, and actin cytoskeleton appear to be involved in mediating increased Ca(2+) spiking. Reorganization of the actin microfilaments by a 94 GHz field seems to play a crucial role in modulating not only Ca(2+) activity but also cell biomechanics. Many but not all observed cellular responses to MMW were similar to thermally induced effects. For example, cell exposure to a 94 GHz field induced nitric oxide production in some morphologically distinct neuronal cells that could not be reproduced by thermal heating of the cells up to 42 degrees C. The highest observed average temperature rise in the MMW exposure chamber was approximately 8 degrees C above the room temperature, with possible complex non-uniform microscopic distribution of heating rates at the cell level. Our findings may be useful to establish quantitative molecular benchmarks for elucidation of nociception mechanisms and evaluation of potential adverse bioeffects associated with MMW exposure. Moreover, control of Ca(2+) dynamics by MMW stimulation may offer new tools for regulation of Ca(2+)-dependent cellular and molecular activities, for example, in tissue engineering applications.

Bioelectromagnetics. 1997;18(4):324-34.

Search for frequency-specific effects of millimeter-wave radiation on isolated nerve function.

Pakhomov AG, Prol HK, Mathur SP, Akyel Y, Campbell CB.

Microwave Bioeffects Branch, U.S. Army Medical Research Detachment of the Walter Reed Army Institute of Research, Brooks Air Force Base, San Antonio, Texas 78235-5324, USA.

Abstract

Effects of a short-term exposure to millimeter waves (CW, 40-52 GHz, 0.24-3.0 mW/cm2) on the compound action potential (CAP) conduction were studied in an isolated frog sciatic nerve preparation. CAPs were evoked by either a low-rate or a high-rate electrical stimulation of the nerve (4 and 20 paired pulses/s, respectively). The low-rate stimulation did not alter the functional state of the nerve, and the amplitude, latency, and peak latency of CAPs could stay virtually stable for hours. Microwave irradiation for 10-60 min at 0.24-1.5 mW/cm2, either at various constant frequencies or with a stepwise frequency change (0.1 or 0.01 GHz/min), did not cause any detectable changes in CAP conduction or nerve refractoriness. The effect observed under irradiation at a higher field intensity of 2-3 mW/cm2 was a subtle and transient reduction of CAP latency and peak latency along with a rise of the test CAP amplitude. These changes could be evoked by any tested frequency of the radiation; they reversed shortly after cessation of exposure and were both qualitatively and quantitatively similar to the effect of conventional heating of 0.3-0.4 degree C. The high-rate electrical stimulation caused gradual and reversible decrease of the amplitude of conditioning and test CAPs and increased their latencies and peak latencies. These changes were essentially the same with and without irradiation (2.0-2.7 or 0.24-0.28 mW/cm2), except for attenuation of the decrease of the test CAP amplitude. This effect was observed at both field intensities, but was statistically significant only for certain frequencies of the radiation. Within the studied limits, this effect appeared to be dependent on the frequency rather than on the intensity of the radiation, but this observation requires additional experimental confirmation.

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