Dynamical Probing of the Mechanisms Underlying Calcium Oscillations

Abstract

Oscillations in the concentration of free intracellular calcium ([Ca2+]) play an important role in many cell types. Thus, understanding the mechanisms underlying Ca2+ oscillations is of significant scientific import. There are two basic classes of mechanism that cause these oscillations: (1) positive and negative feedback from calcium to the inositol trisphosphate (IP3) receptor, and (2) positive and negative feedback from calcium to IP3 metabolism. These two classes can be distinguished experimentally by their different responses to pulses of IP3. In general most cells will have both types of mechanism present simultaneously. We show that, when Ca2+ oscillations are driven by these two mechanisms at the same time, one mechanism is dominant. As the strength of each mechanism is varied, the response of the cell exhibits a threshold phenomenon, being governed either by one mechanism or the other, with no ambiguity in the response to a pulse of IP3. We interpret these results, and other responses to IP3 pulses, in terms of a fast-slow time scale analysis of the calcium dynamics, where calcium transport across the cell membrane occurs on a slow time scale.