PMID- 37981761
OWN - NLM
STAT- MEDLINE
DCOM- 20231222
LR  - 20240331
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 122
IP  - 24
DP  - 2023 Dec 19
TI  - An integrate-and-fire approach to Ca(2+) signaling. Part II: Cumulative 
      refractoriness.
PG  - 4710-4729
LID - S0006-3495(23)00715-4 [pii]
LID - 10.1016/j.bpj.2023.11.015 [doi]
AB  - Inositol 1,4,5-trisphosphate-induced Ca(2+) signaling is a second messenger 
      system used by almost all eukaryotic cells. The agonist concentration stimulating 
      Ca(2+) signals is encoded in the frequency of a Ca(2+) concentration spike 
      sequence. When a cell is stimulated, the interspike intervals (ISIs) often show a 
      distinct transient during which they gradually increase, a system property we 
      refer to as cumulative refractoriness. We extend a previously published 
      stochastic model to include the Ca(2+) concentration in the intracellular Ca(2+) 
      store as a slow adaptation variable. This model can reproduce both stationary and 
      transient statistics of experimentally observed ISI sequences. We derive 
      approximate expressions for the mean and coefficient of variation of the 
      stationary ISIs. We also consider the response to the onset of a constant 
      stimulus and estimate the length of the transient and the strength of the 
      adaptation of the ISI. We show that the adaptation sets the coefficient of 
      variation in agreement with current ideas derived from experiments. Moreover, we 
      explain why, despite a pronounced transient behavior, ISI correlations can be 
      weak, as often observed in experiments. Finally, we fit our model to reproduce 
      the transient statistics of experimentally observed ISI sequences in stimulated 
      HEK cells. The fitted model is able to qualitatively reproduce the relationship 
      between the stationary interval correlations and the number of transient 
      intervals, as well as the strength of the ISI adaptation. We also find positive 
      correlations in the experimental sequence that cannot be explained by our model.
CI  - Copyright (c) 2023 Biophysical Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Ramlow, Lukas
AU  - Ramlow L
AD  - Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany; 
      Department of Physics, Humboldt University Berlin, Berlin, Germany; Max Delbruck 
      Center for Molecular Medicine, Berlin, Germany.
FAU - Falcke, Martin
AU  - Falcke M
AD  - Department of Physics, Humboldt University Berlin, Berlin, Germany; Max Delbruck 
      Center for Molecular Medicine, Berlin, Germany. Electronic address: 
      martin.falcke@mdc-berlin.de.
FAU - Lindner, Benjamin
AU  - Lindner B
AD  - Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany; 
      Department of Physics, Humboldt University Berlin, Berlin, Germany.
LA  - eng
PT  - Journal Article
DEP - 20231119
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
SB  - IM
MH  - *Neurons/physiology
MH  - *Models, Neurological
MH  - Signal Transduction
MH  - Action Potentials/physiology
PMC - PMC10754692
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/11/20 06:54
MHDA- 2023/12/22 06:42
PMCR- 2024/12/19
CRDT- 2023/11/20 03:56
PHST- 2023/07/25 00:00 [received]
PHST- 2023/10/20 00:00 [revised]
PHST- 2023/11/15 00:00 [accepted]
PHST- 2024/12/19 00:00 [pmc-release]
PHST- 2023/12/22 06:42 [medline]
PHST- 2023/11/20 06:54 [pubmed]
PHST- 2023/11/20 03:56 [entrez]
AID - S0006-3495(23)00715-4 [pii]
AID - 10.1016/j.bpj.2023.11.015 [doi]
PST - ppublish
SO  - Biophys J. 2023 Dec 19;122(24):4710-4729. doi: 10.1016/j.bpj.2023.11.015. Epub 
      2023 Nov 19.