Temperature-Mediated Effects of Millimeter Wave Stimulation on Membrane Protein Function

Abstract

Despite numerous demonstrations that millimeter waves (MMW) induce changes in cellular activity in neuronal and muscle preparations, the mechanisms underlying these changes remain unclear. Given the high aqueous absorbance at millimeter wavelengths, thermal mechanisms are likely. However, non-thermal mechanisms based on resonant effects have also been postulated. We examined the effects of MMW stimulation in a simplified preparation comprising Xenopus laevis oocytes expressing canonical ion channels and transporters that underlie membrane excitability. Oocytes were injected with RNA encoding the Drosophila voltage-gated potassium channel Shaker, the rat voltage-gated sodium channel NaV1.4 with its β1 subunit, a mixture of the α and β1 subunits of the squid sodium-potassium pump, or an “AP mix” of the Shaker and NaV1.4 channels enabling action potential (AP) generation. Electrophysiological responses to MMW were studied using two electrode voltage and current clamps. In this system, MMW (0 to 170 mW/cm2 at 60 GHz) applied directly to oocytes via a home-built waveguide setup produced local temperature increases of 0.5 to 5° C on a timescale of 1-10 seconds. MMW radiation altered Shaker activation kinetics and voltage dependence and NaV1.4 inactivation kinetics and voltage dependence. MMW also accelerated the activity of the sodium-potassium pump. In AP mix-injected oocytes, the AP firing rate under current clamp increased with the increasing power of applied MMW, and higher power led to truncated AP trains. The observed effects of MMW on ion channels and transporters are consistent with purely thermal effects. Likewise, changes in AP firing are predicted by thermal dependencies in the Hodgkin and Huxley model. Our results suggest that MMW stimulation produces significant thermally-mediated effects on excitable cells that must be taken into account in the study and use of this range of wavelengths in biology and medicine.