Response of membrane-associated calcium signaling systems of the cell to extremely low-frequency external signals with different waveform parameters

The theoretical analysis of responses of calcium-dependent membrane-associa ted 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). Calciu m channels of the plasma membrane were chosen as the target for the influen ce of external periodic signals. The effect of external signals was manifes ted as an increase in average [Ca2+](i) at certain parameters of the signal s. The effect had a threshold dependence on the relative amplitude of the e xternal signal. The effect character was shown to depend strongly on a sequ ence of delivery of the external stimuli. The effect also depended on the p hase of the influencing signal with respect to the moment of the chemical s timulation 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 w hich the signal amplitude exceeded a certain threshold value. The presence of negative amplitudes, i.e., variation of the rate of calcium signaling pr ocess around an inherent value, played an important role for the effect cha racteristics. To ensure a regimen for the optimal effect, it is necessary f or the external signal parameters to be interrelated with characteristics o f transient processes during the system's response to an intensive chemical stimulus. Results of theoretical analysis led us to the conclusion that th e signal waveform parameters, which are determined not only by frequency sp ectrum, but also by initial phase of each frequency component, play a major role in the revelation and development of the biological system response t o an external electromagnetic signal.