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Adv Exp Med Biol. 2020;1131:799-826. doi: 10.1007/978-3-030-12457-1_32.

A Statistical View on Calcium Oscillations.

Author information

1
Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham, UK.
2
Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
3
Department of Physics, Humboldt University, Berlin, Germany.
4
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.
5
National Biomedical Computation Resource, University California San Diego, La Jolla, CA, USA.
6
School of Life Sciences, University of Nottingham, Nottingham, UK.
7
Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham, UK. ruediger.thul@nottingham.ac.uk.

Abstract

Transient rises and falls of the intracellular calcium concentration have been observed in numerous cell types and under a plethora of conditions. There is now a growing body of evidence that these whole-cell calcium oscillations are stochastic, which poses a significant challenge for modelling. In this review, we take a closer look at recently developed statistical approaches to calcium oscillations. These models describe the timing of whole-cell calcium spikes, yet their parametrisations reflect subcellular processes. We show how non-stationary calcium spike sequences, which e.g. occur during slow depletion of intracellular calcium stores or in the presence of time-dependent stimulation, can be analysed with the help of so-called intensity functions. By utilising Bayesian concepts, we demonstrate how values of key parameters of the statistical model can be inferred from single cell calcium spike sequences and illustrate what information whole-cell statistical models can provide about the subcellular mechanistic processes that drive calcium oscillations. In particular, we find that the interspike interval distribution of HEK293 cells under constant stimulation is captured by a Gamma distribution.

KEYWORDS:

Bayesian inference; Calcium spikes; Heterogeneous cell populations; Intensity functions

PMID:
31646535
DOI:
10.1007/978-3-030-12457-1_32
[Indexed for MEDLINE]

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