Work

A Ca2+ puff model based on integrodifferential equations

Year: 2025

Type: article

Abstract: The calcium signalling system is important for many cellular processes within the human body. Signals are transmitted within the cell by releasing calcium (Ca $$^{2+}$$ 2 + ) from the endoplasmic reticulum (ER) into the cytosol via clusters of Ca $$^{2+}$$ 2 + channels. Mathematical models of Ca $$^{2+}$$ 2 + release via inositol 1,4,5-trisphosphate receptors (IP3R) are used to compute Ca $$^{2+}$$ 2 + transients in regions that are difficult to measure directly. In particular, accounting for the data on Ca $$^{2+}$$ 2 + puffs as stochastic Ca $$^{2+}$$ 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 $$^{2+}$$ 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 $$^{2+}$$ 2 + concentrations we succeed in generating realistic Ca $$^{2+}$$ 2 + puffs. By interpreting the integral term as a weighted average of Ca $$^{2+}$$ 2 + concentrations that extend over a time interval of length $$\tau $$ τ into the past we conclude that the IP3R requires a certain amount of memory of past ligand concentrations.

Source: Journal of Mathematical Biology

DOI: 10.1007/s00285-025-02202-3

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

Institutions: Liverpool John Moores University, The University of Melbourne, AstraZeneca (United Kingdom), University of Auckland, University of Liverpool

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,090

Funder: Liverpool John Moores University