A Ca² puff model based on integrodifferential equations: A Ca² puff model based on integrodifferential equations: M. Hawker et al.

Hawker, Molly; Cao, Pengxing; Kelly, Ross A.; Sneyd, James; Siekmann, Ivo

The calcium signalling system is important for many cellular processes within the human body. Signals are transmitted within the cell by releasing calcium (Ca 2 ) from the endoplasmic reticulum (ER) into the cytosol via clusters of Ca 2 channels. Mathematical models of Ca 2 release via inositol 1,4,5-trisphosphate receptors (IP3R) are used to compute Ca 2 transients in regions that are difficult to measure directly. In particular, accounting for the data on Ca 2 puffs as stochastic Ca 2 release events in models remains challenging. Parameterising Markov models for representing the IP3R with steady-state single channel data obtained at fixed combinations of the ligands Ca 2 and inositol-trisphosphate (IP3) has previously been demonstrated to be insufficient. However, by extending an IP3R model based on steady-state data with an integral term that incorporates the delayed response of the channel to varying Ca 2 concentrations we succeed in generating realistic Ca 2 puffs. By interpreting the integral term as a weighted average of Ca 2 concentrations that extend over a time interval of length τ into the past we conclude that the IP3R requires a certain amount of memory of past ligand concentrations.

Journal of Mathematical Biology, 2025, Vol 90, Issue 4, p1

0303-6812

Academic Journal

10.1007/s00285-025-02202-3