RESPONSE OF MEMBRANE-ASSOCIATED CALCIUM SIGNALING SYSTEMS OF THE CELL TO EXTREMELY LOW-FREQUENCY EXTERNAL SIGNALS WITH DIFFERENT WAVEFORM PARAMETERS

Abstract

The theoretical analysis of responses of calcium-dependent membrane-associated signaling systems to weak extremely low-frequency periodic signals with different waveform parameters was performed on a model suggested recently (Gapeyev and Chemeris, Electro- and Magnetobiology 19, 21–42, 2000). Calcium channels of the plasma membrane were chosen as the target for the influence of external periodic signals. The effect of external signals was manifested as an increase in average [Ca²⁺]_i at certain parameters of the signals. The effect had a threshold dependence on the relative amplitude of the external signal. The effect character was shown to depend strongly on a sequence of delivery of the external stimuli. The effect also depended on the phase of the influencing signal with respect to the moment of the chemical stimulation of the cell. Under the influence of sine-wave, rectangular, and sawtooth external signals, amplitude- and phase-frequency “windows” of the rise in average [Ca²⁺]_i were revealed. Locations of amplitude-frequency “windows” and phase-frequency characteristics of the effect were determined by “the width of effective range of the signal,” that is, the time during which the signal amplitude exceeded a certain threshold value. The presence of negative amplitudes, i.e., variation of the rate of calcium signaling process around an inherent value, played an important role for the effect characteristics. To ensure a regimen for the optimal effect, it is necessary for the external signal parameters to be interrelated with characteristics of transient processes during the system's response to an intensive chemical stimulus. Results of theoretical analysis led us to the conclusion that the signal waveform parameters, which are determined not only by frequency spectrum, but also by initial phase of each frequency component, play a major role in the revelation and development of the biological system response to an external electromagnetic signal.