COMPLEX INTRACELLULAR CALCIUM OSCILLATIONS - A THEORETICAL EXPLORATION OF POSSIBLE MECHANISMS

Intracellular Ca2+ oscillations are commonly observed in a large numbe r of cell types in response to stimulation by an extracellular agonist . In most cell types the mechanism of regular spiking is well understo od and models based on Ca2+-induced Ca2+ release (CICR) can account fo r many experimental observations. However, cells do not always exhibit simple Ca2+ oscillations. In response to given agonists, some cells s how more complex behaviour in the form of bursting, i.e. trains of Ca2 + spikes separated by silent phases. Here we develop several theoretic al models, based on physiologically plausible assumptions, that could account for complex intracellular Ca2+ oscillations. The models are al l based on one- or two-pool models based on CICR, We extend these mode ls by (i) considering the inhibition of the Ca2+-release channel on a unique intracellular store at high cytosolic Ca2+ concentrations, (ii) taking into account the Ca2+-activated degradation of inositol 1,4,5- trisphosphate (IP3), or (iii) considering explicitly the evolution of the Ca2+ concentration in two different pools, one sensitive and the o ther one insensitive to IP3. Besides simple periodic oscillations, the se three models can all account for more complex oscillatory behaviour in the form of bursting. Moreover, the model that takes the kinetics of IP3 into account shows chaotic behaviour.