Quantal release, incremental detection, and long-period Ca2+ oscillations in a model based on regulatory Ca2+-binding sites along the permeation pathway.
Quantal release, incremental detection, and oscillations are three types of Ca2+ responses that can be obtained in different conditions, after stimulation of the intracellular Ca2+ stores by submaximum concentrations of inositol 1,4,5-triphosphate (InsP3). All three phenomena are thought to occur through the regulatory properties of the InsP3 receptor/Ca2+ channel. In the present study, we perform further analysis of the model (Swillens et al., 1994, Proc. Natl. Acad. Sci. USA. 91:10074-10078) previously proposed for transient InsP3-induced Ca2+ release, based on the bell-shaped dependence of the InsP3 receptor activity on the Ca2+ level and on the existence of an intermediate Ca2+ domain located around the mouth of the channel. We show that Ca2+ oscillations also arise in the latter model. Conditions for the occurrence of the various behaviors are investigated. Numerical simulations also show that the existence of an intermediate Ca2+ domain can markedly increase the period of oscillations. Periods on the order of 1 min can indeed be accounted for by the model when one assigns realistic values to the kinetic constants of the InsP3 receptor, which, in the absence of a domain, lead to oscillations with periods of a few seconds. Finally, theoretical support in favor of a positive cooperativity in the regulation of the InsP3 receptor by Ca2+ is presented.
Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Brussels, Belgium. gdupont@ulb.ac.be
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Swillens
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009991:Oscillometry; D011789:Quantum Theory; D013997:Time Factors
D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium