The frequency encoding of pulsatility.
Examples of pulsatile signalling abound in intercellular communication, suggesting that this phenomenon represents a major function of biological rhythms. Pulsatile signals can be encoded in terms of their frequency and prove more efficient than monotonous ones whenever constant stimulation induces desensitization of target cells. We address the main examples of frequency encoding of pulsatility, besides those of neuronal nature. Considered in turn are cAMP oscillations in the slime mould Dictyostelium discoideum, the pulsatile secretion of hormones such as gonadotropin-releasing hormone or growth hormone, intracellular Ca2+ oscillations, and circadian rhythms. Models based on receptor desensitization show the possibility of optimizing cellular responses to cAMP signals in Dictyostelium or to pulsatile hormonal stimulation. The models indicate how the optimal duration of the pulsatile signal and the optimal interval between successive pulses vary as a function of the rates or receptor desensitization and resensitization and of the maximum ligand level during stimulation. The frequency encoding of intracellular Ca2+ oscillations appears to rely on another molecular mechanism. Models based on protein phosphorylation by a Ca(2+)-calmodulin activated kinase show that the mean level of phosphorylated protein increases with the frequency of calcium spikes--which itself rises with the degree of stimulation--and that distinct levels of different phosphorylated proteins can be reached for a Ca2+ signal of given frequency.
Goldbeter
A
A
Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Belgium.
Dupont
G
G
Halloy
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D004023:Dictyostelium / Q000378:metabolism; D006728:Hormones / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D006728:Hormones; D000242:Cyclic AMP; D002118:Calcium